Singh BN. Effect of food on clinical pharmacokinetics. Clin Pharmacokinet

1999;37:213-20. ,

Wacher VJ, Silverman JA, Zhang Y, Benet LZ. Role of P-glycoprotein and

Cytochrome P450 3A in limiting oral absorption of Peptides and

Peptidomimetics. J Pharm Sci 1998; 87: 1322- 30.

Kumar ON. Surapaneni S. Role of drug metabolism in drug discovery and

development. Med Res Rev 2001 ; 21 : 397-41 1.

Prentis RA, Lis Y, Walker SR. Pharmaceutical innovation by the seven UK-

owned pharmaceutical companies (1964-1985). Br J Clin Pharmacol1988;

25: 387-96.

Delzenne NM. Verbeeck RK. Interactions of food and drug metabolism. J

Pharm Belg 2001; 56: 33-7.

Sundberg MI, Oscarson M. Mc Lellan RA. Polymorphic human cytochrome

P 450 enzymes: an opportunity for individualized drug treatment. TIPS

1999; 20: 342-9.

Shimada T, Martin MV. Pruess-Schuetz D, Mamett LJ, Guengerich FP. Roles

of individual human cytochrome P-450 enzymes in the bioactivation of benzo

(a) pyrene, 7,8-dihydroxy-7, 8-dihydrobenzo (a) pyrene, and other

dihydrodiol derivatives of polycyclic aromatic hydrocarbons. Cancer Res

1989; 49: 6304-12.

Stoilov I. Jansson I, Sarfarazi M, Schenkman JB. Roles of cytochrome p450

in development. Drug Metaboi Drug Interact 2001; 18: 33-55.

Rebberck TR, Jaffe JM, Walker AH, Wein AJ, Malkowicz SB. Modification

of clinical presentation of prostate tumors by a novel genetic variant in

CYP3A4. J Natl Cancer inst 1998; 90: 1225-9.

Felix CA. Walker AH, Lange BJ, Williams TM. Winick NJ. Cheung NK, et

ai,. Association of CYP3A4 genotype with treatment-related leukemia. Proc

Natl Acad Sci USA 1998; 95: 13176- 81.

Shimada T. Yamazake H, Mimura M, lnui Y, Guengerich FP. Interindividual

variations in human liver cytochrome P 450 enzymes involved in the oxida-

tion of drugs, carcinogens and toxic chemicals: studies with liver mi-

crosomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther

1994; 270: 414-23.

Watkins PB, Wrighton SA, Schuetz EG. identification of glucocortiwids-

inducible cytochrome P 450 in the intestinal mucosa of rats and man. J

Clin invest 1987; 80: 1029-36.

Wacher VJ, WU CY, Benet LZ. Overlapping substrate specificities and tis-

sues distribution of cytochrome P450 3A4 chemotherapy. Mol Carcinog

1995; 13: 129-34.

Wacher VJ, Salphati L, Benet LZ. Active secretion and enterocytic drug

metabolism barriers to drug absorption. Adv Drug Delivery Rev 1996; 20:

99-1 12.

Hashirnoto H, Toide K, Kitamura R. Fujita M. Tagawa S, itoh S. Kamataki T.

Gene structure of CYP3A4 and adult-specific form of cytochrome P 450 in

human livers and its transcriptional control. EurJ Biochem 1993; 218: 585-

95.

Schuetz JD. Beach DL, Guzelian PS. Selective expression of cytochrome

P 450 CYP3A mRNA in embryonic and adult human liver. Phanacogenitics

1994; 4: 11-20.

Koiars JC. Lown KS. Schmiedlin-Ren P. Ghosh M, Fang C, eta/.. CYP3a

gene expression in human gut epithelium. Phanacogentics 1994; 4: 247-

59.

Koiars JC, Schmiedlin-Ren P, Schuetz JD. Fang C, Watkins PB. identifica-

tion of rifampin- inducible P450111A4 (CYP3A4) in human small bowel

enterocytes. J Ciin invest 1992; 90: 1871-8.

Lown KS, Ghosh M, Watkins PB. Sequences of intestinal and hepatic cyt*

chrome P 450 3A4 cDNAs are identical. D N ~ Metab Dispos 1998; 26: 185-7.

Paine MF. Shen DD, Kunze KL. First pass metabolism of midazolam by the

human intestine. Clin Phanacol Ther 1998; 60: 14-24.

Paine MF, Khalighi M, Fisher JM, Shen DD, Kunze KL. et ai.. Characteriza-

tion of interintestinal and intraintestinal variations in human CYP3A-de-

pendent metabolism. J Pharmacol Exp Ther 1997; 283: 1552-62.

Kolan JC. Awni WM, Merion RM, Watkins PB. First pass metabolism of

cydosporin by the gut. The Lancet 1991; 338: 1488-90.

Borot P, Schinkel AH, Smlt JJM, Wagener E, Van Deemter L, S q t h AJ, et

el,. Ciasslcai and novel forms of muitidrug resistance And the physiological

functions of Pglywprotein in mammals. Phamacol Ther 1993; 60: 289-

99.

Gottesman MM, Pastan I. Biochemistry of multidrug resistance mediated

by the multidrug transporter. Annu Rev Biochem 1993; 82: 385-427.

Hsing S, Gatmaitan 2, Arias IM. The function of Gp 170, the muitidrug-

resistance gene product, in the brush border of rat intestinal mucosa. Gas-

troenterology 1992; 102: 879-85.

Tsuji A, Tamai I. Carrier-mediated intestinal transport of drugs. Pharm Res

1997; 13: 963- 77.

Fojo AT, Ueda K, Slamon DJ, Poplack DO, Gottesman MM, Pastan I. Ex-

pression of a multidrug-resistance gene in human tumors and tissues. Proc

Natl Acad Sci USA 1987; 84: 265-9.

Thiebaut F, Tsururo T, Hamada H, Gottesman MM. Pastan I. Wiliingham

MC. Cellular localization of the multidrug resistance gene product Pglyw-

protein in normal human tissues. Proc Natl AcadSci USA 1987; 84: 7735-

8.

Lados SD. Hairtos DN. Raptis SA. Honey may have a laxative effect on

normal subjects because of incomplete fructose absorption. Am J clin Nub

1995; 82: 1212-5.

Trease GE. Evans WC. Carbohydrates. Oxford: ELBS publishers, 1985:

345-9.

Molan PC. The antibacterial activity of honey. 1. The nature of the antibac-

terial activity. Bee World 1992; 73: 5-22.

Wallis TE. Gums and saccharine substances. In: Textbook of Pharmacog-

nosy. New Delhi: CBS publishers and distributors, 1998: 479-82.

Al-Swayeh OA, Aii ATMM. Effect of ablation of capsaicin-sensitive neurons

on gastric protection by honey and sucralfate.. Hepatogastroenteroiogy

1998; 45: 297-301.

Fotidar MS. Lotus honey. Indian Bee J 1945; 7: 102-7.

Ankra-Badu GA. Sickle cell leg ulcers in Ghana. East Afr Med J 1992; 69:

366-9.

Kandil A, El-Bandy M, Abdel-Wahed K, Abdel-Gawwad M, Fayez M. wra-

tive properties of true floral and false nonfloral honeys on induced gastric

ulcer. J Drug Research (cairo) 1987; 17: 103-6.

Rao CV, Desai D. Rivenson A. Chemopreventlve of colon carcinogenesis

by phenythyl-3- methylcaffeate. Cancer Res 1995; 55: 2310-9.

Wahdan HAL. Causes of the antimicrobial activity of honey. Infection 1998;

28: 26-31.

Allsop KA. Miilor JB. Honey revisited: a reappraisal of honey in pre-indus-

trial diets. Br J Nutr 1996; 75: 513-20.

Naim M. Kare MR. The nutritional significance of sweetness. London: Ap-

plied science publishers, 1982:171-90.

Rumessen JJ. Fructose and related food carbohydrates. Source, absorp-

tion and clinical implications. Scand J Gastroenterol 1992; 27: 819-25.

Ransome HM. The sacred bee in ancient times and folklore. London: George

allen and Unwin publishers, 1937: 25-30.

McGee H. on food and cooking. London: Harper wllins publishers. 1984:

10-20.

Crane E. The archaeology of Beekeeping. New York: corneli University

press, 1983: 32- 40.

Low T. Bush tucker-Australia's wild food harvest. Sydney: Angus and

Robertson, 1989: 60-8.

Cane E. Honey: a Comprehensive survey. London: Heinemman, 1975:

98-106.

Darby WJ, Ghalioungui P. Grivetti L. Food. Thegift of Osiris. London: Aca-

demic press. 197735-16.

Free JB. Bees and Mankind. Boston: George allen and Unwin, 1982: 20-

32.

Style S. Honey: From hive to Honeypot. London: Pavilion, 1992: 12-22.

Wilson CA. Food and drink in Britain: from the stone age to recent times.

London: Constable,l973: 26-32.

Tennahill R. Food in history. St Albans: Paladin, 1975: 15-22.

52. Beck BF. Honey and your health. New York: Mcbride. 1994: 9-16

53. Zumla A. Honey a remedy rediscovered. J R Soc Mad 1989; 82: 384-5.

lmperato PJ. Traditional beliefs about measles and its treatment among

the Bambara of Mali. Trop Gaogr Med 1969; 21: 62-7.

Moian PC. Why honey is effective as a medicine.1. Its use in modern medi-

cine. Bee world 1999; 80: 80-92.

Aristotie. Historia Animalium. Oxford. UK: Oxford University. 1910: 16-35.

Forrest RD. Early history of wound treatment. J R Soc Med 1982; 75: 198- 205.

Lados SD, Raptis SA. Honey, fructose absorption and the laxative effect.

Nutrition 1999;15:591-2.

Allan KL. A Survey of the antibacterial activity of some New Zealand hon-

eys. J Pharm Pharmacol1991; 43: 81 7-22.

Thompson WAR. Herbs that heal. J R College Gan Practi 1976; 26: 365-

70.

Kauffrnan GB. Chemophobia. Chemistry in Britain 1991; 3: 512-6.

Soffer A, Chihuahuas L. Chelation therapy, and honey from Boulder, Colo.

Arch Intern Med 1976; 136: 865-6.

Editorial. Honey: sweet and dangerous or panama? South African Madi-

cal Journal 1974; 56:2300-9.

Condon RE. Curious interaction of bugs and bees. Surgery 1993; 113:

234-5.

Biornfieid R. Honey for decubitus ulcers. J A M A 1973; 224: 905-5.

Hutton DJ. Treatment of pressure sores. Nursing Times 1966; 62: 15334.

Wadi M, Al-Arnin H. Farouq A, Kashef H, Khaied SA. Sudanese bee honey

in the treatment of supportive wounds. Arab Medico 1987; 3: 16-8.

Efem SEE. Clinical observations on the wound healing properties of honey.

Br J Surgery 1988; 75: 679-81.

Phuapradit W. Saropala N. Topical application of h y e y in t r w e n t of

abdominal wound disruption. Aust N Z J Obstet Gynaecol1992; 32: 3814.

Seymour FI, West KS. Honey - Its role in medicine. Medical Times 1951; 79: 104-7.

Yang KL. The use of honey in the treatment of chilblains, non-specific ul-

cers, and small wounds. Chin Med J 1944; 62: 55-60.

Tovey FI. Honey and Healing. J R Soc Med 1991; 84: 447-50.

Farouk A, Hassan T, Kashif H. Khalid SA, Mutawali I, Wadi M. Studies on

Sudanese bee honey: laboratory and clinical evaluation. InterJ Crude Drug

Research 1988; 28: 161 -8.

Lcke H. Wundbehandlung mit Honig und Lebertran. Deutsche Medizinische

Wochenschrift 1935; 61: 1638-40.

Green AE. Wound healing properties of honey. Br J Surg 1988; 75: 1278 - 82.

Braniki FJ. Surgery in Western Kenya. Ann Royal College surgeon Eng

1981; 63: 348-52.

Mcinerney RJF. Honey- a remedy rediscovered. J R Soc Med 1990; 83:

127-35.

Wood B. Rademaker M, Molan PC. Manuka honey, a low cost leg ulcer

dressing. N Z Med J 1997; 110: 107 - 15.

Descottes B. De la ruche a I'hospital ou I'utilisation du rniel dans I'unitE de

soins. L'ebeille de France et I'apicukure 1990; 754: 459-60.

Burlando F. Suil'azione terapeutica del miele nelle ustioni. Minerva

Dematologica 1978; 113: 694706.

Bergman A, Yanai J, Weiss J, Bell D, David MP. Acceleration of wound

healing by topical application of honey. An animal model. Am J Surg 1983;

145: 374-6.

Harris S. Honey for the treatment of superficial wounds: a case report and

review. Prim Intention 1994; 2: 18-23.

Subrahmanyam M. Honey impregnated g a u e versus polyurethane film in

the treatment of bums- a prospective randomized study. Br J Plastic Sur

1993; 46: 322-3.

Subrahmanyam M. Toplcal application of horny in t m i h e n t of b%s. BrJ

Sur 1991; 7d: 497-8.

Postmes TJ, Bosch MMC, Dutrieux R. Van Baare J, Hoekstra MJ. Speed-

ing up the healing of burns with honey. An experimental study with histo-

logical assessment of wound biopsies. New York: plenum press, 1007: 27-37.

Gupta SK, Singh H, Vanhney AC. Prakash P. Therapeutic efficacy of honey

in infected wounds in buffaloes. Indian J Animal Sci 1992; 62: 521-3.

Somerfield SD. Honey and healing. J R Soc Med 1991; 84: 179 - 87.

Ndayisaba G, Bazira L, Habonimana E. Muteganya D. Clinical and bacte-

riological results in wounds treated with honey. J Ofthop Surg 1993; 7:

202-4.

Bose B. Honey or sugar in treatment of infected wounds? Lancet 1982; 1:

963- 9.

Efem SEE. Recent advances in the management of Fournier's gangrene:

Preliminary observations. Surgery 1993; 113: 200-4.

Subrahmanyam M. A prospective randomized clinical and histological study

of superficial burns wound healing with honey and silver suifadiazine. Bums

1998; 24: 157-61.

Subrahmanyam M. Honey dressing versus boiled potato peel in the treat-

ment of bums: a prospective randomized study. Bums 1996; 22: 491-3.

Dumrongiert E. A follow up study of chronic wound healing dressing with

pure natural honey. J National Res Council of Thailand 1983; 15: 36-66.

Buiman MW. Honey as a surgical dressing. Middlesex Hosp J 1955; 55:

188-9.

Cavanage D. Beazley J. Ostapowiu F. Radical operation for carcinoma of

the vulva. A new approach to wound healing. J Obst and Gynec British

Commonwealth 1970; 77: 1037-40.

Linneti P. Honey for equine diarrhoea. Control and Therapy 1996; 16: 906-

13.

Haffejee iE, Moosa A. Honey in the treatment of infantile gastroenteritis.

BMJ 1985; 2@0:1866-7.

Men'shlkov FK, Feidman Si. Curing stomach ulcers w iq honey. Sqetskaye

Mednsina 1949;10:13-4.

99. Salem SN. Honey regimen in gastrointestinal disorders. Bulletins of Islamic

Medlcine 1981 ; I : 3.58-82.

Ali ATM. Natural honey accelerates healing of indomethacin-induced an-

trai ulcers in rats. Seudi Med Jour 1995; 16: 161-6.

Ali AT. Al-Humayyd MS, Madan BR. Natural honey prevents indomethacin

and ethanol-induced gastric lessions in rats. Saudi Med Jour 1990; 11:

275-9.

Ali AT. Natural honey exerts its protective effects against ethanol-induced

gastric iessions in rats by preventing depletion of glandular nonprotein

sulfhydryls. Trop Gastroenterol. 1995;16: 18-26.

Aii AT. Prevention of ethanol-induced gastric lesions in rats by natural honey,

and its possible mechanism of action. Scand J Gastroenterol 1991; 26:

281-8.

Meier KE. Freitag G. Ber Die antibiotischen Eigenschaften von Sacchariden

und Bienenhonig. Zeitschriff fr Hygiene und lnfektionshrankheiten 1955;

141: 326-32.

Popescu MP. Paios E, Popescu F. Studiul eficacitatii terapiei biologice

compiexe cu produse apicole in unele afectiuni oculare locaiizate palpe-

brai si conjunctival in raport cu modificarile clinico-functionale.. Revista de

Chirurgie Oncologie Rediologie ORL Oftalmologie Stomatologie Seria

Offalmaologie 1985; 29: 53-61.

Osaulko GK. Use of honey in treatment of the eye [in Russian]. Vestnik

Offal'mologii (Moskow) 1953; 32: 35-6.

Badyal DK, Dadhick AP. Cytochrome P 450 and dmg interactions. Indian J

Pharmacol2001; 33: 248-59.

Nelson DR, Koymans L. Kamataki T. Stegeman LL, Feyereisen R. Waxman

DJ et el. P 450 Subfamily: update on new sequence, gene mapping.

accession numbers and nomenclature. Phanacogenetics 1996; 6: 1-42.

Bertz RJ, Granneman OR. Use of in vitro and in vivo data to estimate the

likelihood of metabolic pharmacokinetic interactions. Clin Pharmacokinet

1997; 32: 210-258.

Levy RH. Cytochrome P 450 isoenzyme and antiepileptic dmg in@actions.

Epllepsia 1995; 36: S8-S13

Dossing M, Pilsgaard H. Rasmussen 8, Poulssen HE. Time course of

phenobarbital and clmetidine mediated changes in hepatic drug metabo-

lism. Eur J Clin Pharmacol. 1983; 25: 215-22.

Olkkola K. Aranko K. Luurila H, Hiller A, Saarnivaara L, Himberg JJ. A

potential hazardous Interaction between erythromycin and midazolam. Clin

Phennecokinat 1993; 53: 298-305.

Michalets EL. Update:clinically significant cytochrome P 450 drug interac-

tions. Pharmacotherapy 1998;18:84-112.

Pirttiaho HI. Sotaniemi EA, Pelkonen RO et el. Hepatic blood flow and drug

metabolism in patients on enzyme inducing anticonvulsants. Eur J clin

Pharmacol 1982;22:441-5.

Grange JM, Winstanley PA. Davis PDO. Clinically significant drug interac-

tions with antituberculosis agents. Drug Saf 1994; 11:242-51.

Schein JR. Cigarette smoking and clinically significant drug interactions.

Ann Phannacother 1995; 29: 113948.

Brouwer KLR. Dukes GE, Powell JR, Influence of liver function on drug

disposition. In Evans WE. Schentag JJ. Jusko WJ eds. Applied

pharmacokinetics. Spokane. WA: Applied Therapeutics, 1993; 1-59.

Heimark LD, Wienkers L. Dunze K et al. The mechanism of the interaction

between amiodarone and warfarin in humans. Clin Pharmacol Ther

1992;51:398-407.

Ereshefsky L. Riesenman C, Lam YW. Serotonin selective reuptake inhibi-

tor drug interaction and the cytochrome P 450 system. J Clin Psychiatry

996; 57:17-25.

Slaughter RL. Edwards DJ. Recent advances; the cytochrome P 450 en-

zyme. Ann Phannacother 1995;29: 61 9-24.

Schuetz EG. Schuetz JD. Grogan WM. Naray-Fejes-Toth A, Fejes -Toth G

et a/. Expression of cytochrome P 450 3A in amphibian, rat and human

kidney. Arch. Biocham. Biophys 1992; 294: 206-14

Kharasch ED, Thummel KE. Human alfentanil metabolism by cytochrome

P450 3A314. An explanation for the interindividual variability in alfentanil

clearance?. Anesth Anal 1993;76:1033-9.

Venkatakrishnan K, Greenbiatt DJ, von Moitke LL. Shader Ri. Aiprazoiam

is another substrate for human cytochrome P450-3A isoforms. J clin

Psychophamacol 1998; 18:256-61.

Woosley. RL. Cardiac actions of antihistamines. Annu Rev Pharmacol

Toxic01 1996;38:233-52.

Kantola T, Kivisto KT, Neuvonen PJ. Effect of itraconazole on the

pharrnacokinetiw of atowastatin. Clin Phamacol ther 1998; 64: 56-65.

Kivisto KT. Lamberg TS, Kantola T. Neuvonen PJ. Plasma buspirone

concentrations are greatly increased by erythromycin and itraconazole. Clin

Phermecol Ther 1997;62: 348-54.

Tassaneeyakui W, Birkett DJ, Veronese ME. McManus ME, and Tukey RH.

Specificity of Substrate and Inhibitor Probes for Human Cytochromes P450

1Al and lA2. J Pharmacol Exp Ther 1993; 265: 401-7.

Boberg M, Angerbauer R. Fey P, Kanhai WK, Karl W, Kern A, et a/.,

Metabolism of cerivastatin by human iiver microsomes in vitro. Drug Metab

Dispos 1997;25: 321-31.

Wysowski DK, Bacsanyi J. Cisapride and fatal arrhythmia. N Eng J Med

1996;335;290-9.

Rodrigues AD. Roberts EM, Mulford DJ, Yao Y, Ouellet D. Oxidative

metabolism of ciarithromycin in the presence of human iiver microsomes.

Major role for the cytochrome P4503A (CYPBA) subfamily. Drug Metab

Dispos 1997;25:623-30.

Caraco Y, Tateishi T, Guengerich FP. Wood AJJ. Microsomal codeine N-

demthyiation: Cosegregation with cytochrome P4503A4 activity. Drug Meteb

Dispos 1996;24:761-764.

Watkins PB. The role of cytochromes P-450 in cydosporine metabolism. J

Am Acad Dermatol 1990;23:1301-9.

Ducharrne J. Abduilah S. Wainer IW. Dextromethorphan as an in vivo probe

the simultaneous determination of CYP2D6 and CYP3A activity. J

Chromatogr B Biomed Appl1996; 678: 1 13-28

Yesumori T, Nagata K, Yang SK, Chen L-S. Murayama N. Yamazoe Y, Kato

R. Cytochrome P450 mediated metabolism of dlazepam in hum n and rat: 8 Involvement of human CYP2C in N-demethyletion In the substrate-

Gorski JC, Hail SD,' Jones DR. VandenBranden M. Wrighton SA. Regio

selective biotransformation of midazolam by members of the human cyto-

chrome P450 3A (CYP3A) subfamily. Biochem Pharmacol1994;47:1643-

53.

Bailey DG, Arnold MO, Strong A, Munoz C,Spence JD. Effect of grapefruit

juice and naringen on nisoldipine pharmawkinetics. Clin Pharrnacol Ther

1993; 54589-94,

Dixon CM, Coithup PV. Serabjit-Singh CJ, Kerr EM, Boehlert CC, Park GR

et al,. Multiple forms of cytochrome P450 are involved in the metabolism of

ondansetron in humans. Drug Metab Dispos 1995; 23:1225-30.

Desta Z, Kerbusch T. Soukhova N. Richard E. KO JW, Flockhaf? DA. iden-

tification and characterization of human cytochrome P450 isofonns inter-

acting with pimozide. J Phamacol Exp Ther 1998; 285: 428-37.

Tateishi T. Ohashi K, Fujimura A, Ebihara A. The influence of diltiazem

versus cimetidine on propranoiol metabolism. J. Clin. Pham. 1992; 32:1099-

104.

Koley AP. Buters JT, Robinson RC, Markowitz A, Friedman FK. CO binding

kinetics of human cytochrome P450 3A4. Specific interaction of substrates

with kinetically distinguishable wnforrners. J Biol Chern 1995; 2705014-

18.

Koudriakova T, latsimirskaia E. Utkin I. Gangl E, Vouros P. Storozhuk E et

a/.. Metabolism of the human immunodeficiency virus protease inhibitors

indinavir and ritonavir by human intestinal microsomes and expressed cy-

tochrome P4503A413A5: mechanism-based inactivation of cytochrome

P4503A by ritonavir. D N ~ Metab Dispos 1998;26: 552-561.

Manchee GR, Eddershaw PJ, Ranshaw LE, Herriott D, Park GR, Bayliss

MK, eta/,. The aliphatic oxidation of salmeteroi to alpha-hydroxy salmeteroi

in human liver microsomes is catalyzed by cytochmme P450 3A. Dmg Metab

DISPOS 1996;24: 555-9.

Fitzsimmons ME, Collins JM. Selective biotransformation of the human

immunodeficiency virus protease Inhibitor saquinavir by human small-in-

testinai cytochmme P4503A4: potential conttibuUoqto high firslpass me-

tabolism. Dmg Metab Dlspos 1991;25:25656.

Muirhead GJ, Faulkner S, Hamess JA, Taubel J. The effects of steady-

state erythromycin and azithromycln on the pharmacokinetics of sildenafil

in healthy volunteers. Br J Cfin Pharmecol2002;53: 375-435.

Prueksarltanont T. Gorham LM, Ma B. Liu L, Yu X. Zhao JJ et el,. In vitro

metabolism of simvastatin in humans [SBT]identificatlon of metabolizing

enzymes and effect of the drug on hepatic P450s. Drug Meteb Dispos

1997; 25: 1191-9.

Floren LC. Bekersky I, Benet U, Mekki Q, Dressler D, Lee JW et a/,.

Tacrolimus oral bioavailability doubles with madministration of ketownazole.

Clin Pharmecoi Ther 1997;62: 41-49.

Daniels L. Blankson EA, Henderson CJ, Harris AH, Wolf CR, Lennard

MS, et a/. Delineation of human cytochromes P450 involved in the

metabolism of tamoxifen. Br J Clin Pharmacol 1992; 33:153- 60.

Yun CH, Okerholm RA, Guengerich FP. Oxidation of the antihistaminic drug

terfenadine in human liver mlcrosomes. Role of cytochrome P-450 3A(4)

in-dealkylation and C-hydroxylation. Drug Metab Dispos 1993; 21:403-9.

Rotzinger S, Fang J. Baker GB. Trazodone is metabolized to m-

chlorophenylpiperazine by CYP3A4 from human sources. Drug Metab

Dispos 1998;26:572-5.

Zhany Y, Guo X. Lin ET, Benet LZ. Overlapping substrate specificities of

cytochrome P450 3A and P-giywprotein for a novel cysteine protease in-

hibitor. Drug Metab Dispos 1998;26:360-6.

Bohrne A. Ganser A, Hoelzer D. Aggravation of vincristine-induced neuro-

toxicity by itraconazole in the treatment of adult ALL. Ann Hernatol 1995;

71:311-2.

Renwick AB, Mistry H. Ball SE. Walters DG. Kao J, Lake BG. Metabolism

of Zaleplon by human hepatic microsornal cytochrome P450 isoforms.

Xenobiotica 1996;28: 337-48.

Von Moltke LL, Greenblatt DJ, Granda BW, D. Zolpidem metabolism in

v i h : responsible cytochromes, chemical inhibitors, and in vivo wrrelations.

Br J Clin Pharmacoll999; 48: 89-97.

Relling MV, Nemec J. Schuetz EG, Schuetz JD. Gopzalez FJ.aofzekwa

KR. CYP3A substrates. Molphermacol 1994; 45: 352-8.

Aoyama 1, Yamano S, Waxman DJ, Lapenson DP, Meyer UA, Fischer V et

al,. Cytochrome P 460 h PCN3, a novel cytochrome p 450 111 A gene prod- uct that is differentially expressed in adult human liver. cDNA and deduced

amino acid sequence and distinct specificities of ~DNA-expressed hPCNl

and hPCN3 for the metabolism of steroid. J 6/01 Chem 1989; 264:10388- 95.

Schuetz EG, Schinkel AH, Relling MV, Schuetz D. P-giycoprotein: A major determinant of rifampicin-inducible expression of cytochrome P 4503A in mice and humans. Proc Net1 Acad Sci USA 1996; 93: 4001-5.

Anzenbacherova E, Bec N, Anzenbacher P. Hudecek J, Soucek P. Jung C,

etal,. Flexibility and stability of the structure of cytochrome P 450 3A4 and

BM-3. Eur J Blochem 2000; 267: 2916-20.

Schuetz EG, Schuetz JD, Strom SC, Thompson MT, Fisher RA, Molowa

DT et al,. Regulation of human liver cytochrome P450 in family 3A in pri- mary and continuous culture of human hepatocytes. Hepatology 1993; 18: 1254-62.

Lamberg TS, Kivisto KT, Neuvonen PJ. Concentration and effects of

buspirone are considerably reduced by rifampicin. Br J Clin Phannacol

1998; 45381 -5.

Robertson P. DeCory HH, Madan A. Parkinson A. In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinii. Drug

Metab Dispos 2000; 28: 664-71.

Stephen C. Pisciteili, Aaron H. Burstein, Doreen Chaitt, Raui M et a/,.

lndinavir concentrations and St. John's wort. The Lancet 2000; 355: 547-

8.

Kaplan B. Friedman G. Jawbs M, Viscuso R. Lyman N. DeFranco P et a/,.

Potential interaction of troglitazone and cyclosporine. Transplantation 1998;65:1399-1400.

Lewis DFV, Eddershaw PJ. Goldfarb PS. Tarbit MH. Molecular modelling of

CYP3A4.from an alignment with CYPlO2: Identification of key interactions

between putative active site residues and CYP3A-specific chemicals.

Xenobiotics 1996;26: 1067-87.

Ng PW, Chan WK, Chan TY. Torsade de pointes during the dlhcomitant

use of terfenadine and cimetidine. Aust N Z J Med 1996; 26:120-1.

175. Herrlin K, Segerdahl M, Gustafsson LL. Kalso E. Methadone, ciprofloxacin.

and adverse drug reactions. The Lancet 2000; 356: 2069-70.

Tinei M, Descatoire V, Larrey D, Loeper J, Labbe G, Letteron P, Pessayre

D. Effects of ciarithromycin on cytochrome P450. Comparison with other

macroiides. J Pharmacol Exp Ther 1989; 250:746-51.

Court MH, Von Moitke LL, Shader RI, Greenblatt DJ. Biotransformation of

chloroxazone by hepatic microsomes from humans and ten other mamma- lian species. Biopharm Drug Dispos 1997;18: 213-26.

Rasmussen BB, Maenpaa J. Peikonen 0, Lofl S, Poulsen HE, Lykkesfeldt

J et a/,. Selective serotonin reuptake inhibitors and theophylline metabo- lism in human liver microsomes: potent Inhibition by fluvoxamine. Br J Clin

Pharmacol 1995;39:151-60.

Ozdemir M. Aktan Y, Boydag BS, Cingi MI, Musmui A. Interaction between grapefwit juice and diazepam in humans. EurJ Drug Metab Pharmacokinet

1998;23:55-9.

Chiba M, Hensleigh M. Nishime JA. Balani SK, Lin JH. Role of cytochrome

P450 3A4 in human metabolism of MK-639, a potent human immunodefi-

ciency virus protease inhibitor. Drug Matab Dispos 1996; 24307-14.

Gorski JC, Hall SD, Becker P, Affrime MB, Cutler DL, Haehner-Daniels B. In vivo effects of interleukin-10 on human cytochrome P450 activity. Clin

Pharmacol Ther 2000;67:32-43.

Maurice M, Pichard L, Daujat M. Fabre I, Joyeux H. Domergue J, Maurei P.

Effects of imidazole derivatives on cytochmmes P450 from human hepa-

tocytes in primary culture. FASEB J 1992; 6:752-8.

Wandei C. Kim RB. Guengerich FP, Wood AJ . Mibefradii is a P-glycopm-

tein substrate and a potent inhibitor of both P-glycoprotein and CYP3A in

vitro. D N ~ Metab Dispos 2000; 28: 895-8.

He K, Woolf TF. Hoilenberg PF. Mechanism-based inactivation of cytochmme P-450-3A4 by mifepristone. J Pharmacd Exp Ther 1999;286:791-7.

von Moltke LL, Greenblatt DJ, Harmat? JS, Duan SX, Harrei LM. Cotreau- Bibbo MM et el,. Triazolam biotransformation by human liver microsomes in vitro: effects of metabolic inhibitors and dlnical confirmation of a predicted

interaction with ketoconazole. J Pharmacol Exp Thei.1996; 276%0- 9.

Liliibridge JH, Liang BH, Ken BM, Webber S, Quart B, Shetty BV, Lee CA. Characterization of the selectivity and mechanism of human cytochrome

P450 inhibition by the human immunodeficiency virus-protease inhibitor neifinavir mesyiate. Drug Metab Dispos 1998; 26:609-16.

McLeilan RA. Drobitch RK. Monshouwer M, Renton KW. Fiuoroquinolone antibiotics inhibit cytochrome P45O-mediated microsomal drug metabolism

in rat and human. Drug Metab Dispos 1996; 24:1134-8.

Brosen K. Drug Therapy: Fiuoxetine. N Eng J Med 1994; 331:1354-61.

Von Moltke LL, Greenblatt DJ, Grassi JM, Granda BW. Duan SX. Fogelman

SM, eta/,. Protease inhibitors as inhibitors of human cytochromes P450: high risk associated with ritonavir. J Clin Pharrnecol1998; 38:106-11.

Goldstein JA. Clinical relevance of genetic poiymorphisms in the human CYP2C. subfamily. Br J Clin Phannacol2001;52:349-55.

Lamba JK, Dhiman KK. Genetic polymorphism of the hepatic cytochrome P 450C19 in north Indian subjects. Clin Phamacoi Ther 1998; 63: 422-7.

Tanaka E. Update: genetic polymorphism of CYP2Cl9 drug metabolizing enzymes in humans. J Clin Pharrn Ther 1999; 24: 323-9.

Kiose TS. Blaisdeii JA, Goldstein JA., Gene structure of CYP2C8 and extrahepatic distribution of the human CYP2Cs. J Biochem Mol Toxic01

1 Q99;13:289-95.

Shen DD, Kunze KL, Thummel KE. Enzyme-catalyzed processes of first- pass hepatic and intestinal drug extraction. Adv Drug Daliv Rev 1997;27:

99-127.

Venkatakrishnan K, Greenblatt DJ, von Moltke LL, Schmider J. Hannatz

JS, Shader RI. Five distinct human cytochromes mediate amitriptyline N-

demethylation in vitro: dominance of CYP 2C19 and 3A4. Clin Phannacol

1998 38: 11 2-21.

Ketter, T.A. Personal communication with Dr. Terence Ketter about citalopram on March 29. 1995.Flockhart, D.A. 1995.

Bertilsson L, Dahl ML, Tybring G. Pharmacogenetics of antidepressants:

clinical aspects. Acta Psychiatr Scand Suppl 1997; 391:14-21.

Chang TKH, Yu L. Goldstein JA, Waxman DJ. ldent i f icaen of the polymorphically expressed CYP2C19 and the wild-type CYP2C9-ILE"'

allele as low-K, catalysts of cyclophosphamide and ifosfamide activation

Pharmecogenetics $997; 7 :211-21.

Yasumori T, Nagata K, Yang SK, Chen L-S, Murayama N. Yamazoe Y et

a/,. Cytochrome P450 mediated metabolism of diazepam in human and

rat: involvement of human CYP2C in N-demethylation in the substrate concentration-dependent manner. Pharmacogenetics 1993; 3:291-301.

Adedoyin A, Prakash C, O'Shea D, Blair IA, Wilkinson OR. Stereoselective

disposition of hexobarbital and its metabolites: relationship to the S- mephenytoin polymorphism in Caucasian and Chinese subjects. Phar-

rnacogenetics 1994 ; 4: 27-38.

Weaver RJ, Webster D, Melvin W. Dickins M and Burke MD. Human

cytochrome P4502C metabolism. Br J Clin Pharmacol1993;36:167 - 72.

Sohn DR. Kwon JT, Kim HK, lshizaki T. Metabolicdlsposition of lansoprazole in relation to the S-mephenytoin 4'-hydroxylation phenotype status. Clin

Pharmacol Ther 1997;61:574-82.

Wedlund PJ. Aslanian WS, McAllister CB. Wiikinson OR, Branch RA.

Mephenytoin hydroxylation deficiency in Caucasians: frequency of a new oxidative drug metabolism polymorphism. Clin Pharrnacol Ther 1984;

36:773-60.

Kupfer A, Branch RA. Stereoselective mephobarbital hydroxylation

cosegregates with mephenytoin hydroxyiation. Clh Pharmacol Ther, 1985;

36:414-8.

Gram LF, Guentert NV, Grange S, Vistisen K, Brasen K. Moclobemide: a

substrate of CYP2Cl9 and an inhibitor of CYP2Cl9, CYP2D6 and CYPlA2:

A panel study. Clin Phermacol Ther 1995;57:670-7.

Liilibridge JH, Liang BH. Kerr EM. Webber S. Quart B. Shetty BV, Lee CA.

Characterization of the selectivity and mechanism of human cytochrome

P450 Inhibition by the human immunodeficiency vims-protease inhibitor

nelfinavir mesylate. Dmg Metab Dispos 19Q8 ;26:609-16.

Horsmans Y, Lannes D, Larrey D. Tinel M, Letteron P, Loeper J et a/,.

Nilutamlde inhibits mephenytoin Chydroxylatlon in untreated male rats and

in human liver microsomes. Xenobiotfce 1991;21:155Q-70.

Andersson T, Cederberg C, Edvardsson G, Heggelund A, Lundborg P. Ef- fect of omeprazole on diazepam plasma levels in slow versus normal

rapid metabolizers of omeprazoie. Clin Pharmacol Ther 1990;47:79-85.

Tanaka M, Ohkubo T, Otani K, Suzuki A, Kaneko S, Sugawara K et a/,.

Metabolic disposition of pantoprazole, a proton pump inhibitor, in relation

to S-mephenytoin 4'-hydroxyiation phenotype and genotype. Clin Pharmacol

Ther 1997 ;62:619-28.

Bajpai M. Roskos LK. Shen DD, Trager WF. Levy RH. Role of S-mephenytoin

hydroxylase in the metabolism of phenytoin. Pharm Res 1994;ll: 5348 - 552.

Mamiya K. Hadama A. Yukawa E, leiri I. Otsubo K, Ninomiya H et a/,.

CYP2C19 polymorphism effect on phenobarbitone. Pharmacokinetiw in

Japanese patients with epilepsy: analysis by population pharmacokinet-

ics. Eur J C11n Pharrnacoi 2000. 55:821-5.

Yamazaki H. Shimada T. Progesterone and testosterone hydroxylation by

CYP. 2C19, 2C9 and 3A4 in human liver microsomes. Arch Biochern

Biophys 1997; 346: 161-9.

Setiabudy R. Kusaka M. Chiba K, Darmansjah I, lshizaki T. Metabolic Dis-

position of proguanil in extensive and poor metabolizers of S-mephenytoin

4'-hydroxylation recruited from an Indonesian population. Br J Clin

Pharmacol 1995;39:297-303.

Otton SV, Gillam EM. Lennard MS, Tucker GT. Woods HF. Propranoiol

oxidation by human liver microsomes- use of cumene hydroperoxide to

probe isoenzyme specificity and regio- and stereoseiectivity. Br J Clin

Pharmacol 1990 ;30:751-60.

Streetman DS, Bertino JS , Nafiiger AN. Phenotyping of dnrg-metaboiiz-

ing enzymes in adults: a review of in-vivo cytochrome P450 phenotyping

probes. Phanacogenatics 2000; 10: 187-216.

Van der Weide J, Steijns LS. Cytochrome P450 enzyme system: genetic

polymorphisms and impact on clinical pharmacology. Ann Clin Biochern

1999; 36: 722-9.

Breimer DD, Zilly W, Richter E. Influence of wrtiwsteroid on hexobarbital

and tolbutamide disposition. Clin Pharmaml Ther 1978;24:208-12.

Zhou HH. Anthony LB, Wood AJJ, Wilkinson OR. Induction of polymorphic

4'- hydroxyietion of S-mephenytoin by rifampicln. Br J Clin %arrnacol

1990;30:471- 5.

Svensen USH, Asthan M, Hai TN, Bertiison L, Huong DX, Huong NV.

Artemisinin induces omeprazole metabolism in human beings. Clin

Phamacol Ther 1998; 64: 160-167.

Tanaka E. Clinically significant pharmacokinetic drug Interactions between

antiepiieptic drugs. J Clin Pham Ther 1999;24:87-92.

Bajpai M, Roskos LK, Shen DD. Trager WF, Levy RH. Role of S-mephenytoin

hydroxylase in the metabolism of phenytoin. Pham Res 1994, 1l:S348-

S52.

Vandel S, Bertschy G, Baumann P, Bouquet S, Bonin B. Franwis T et el..

Fluvoxamine and fluoxetine: interaction studies with amitriptyiine.

clomipramine and neuroleptics in phenotyped patients. Pharmacol Res 1995

;31:347-53.

Vandel S, Bertschy G. Baumann P, Bouquet S, Bonin B, Francois T et a/..

Fluvoxamine and fiuoxetine: interaction studies with amitriptyiine,

clomipramine and neuroleptics in phenotyped patients. Pharmacol Res

1995;31:347-53.

KO JW, Sukhova N, Thacker D. Chen P, Flockhart DA. Evaluation of

omeprazole and lansoprazoie as inhibitors of cytochrome P450 isoforrns.

Drug Metab Dispos 1997;25:853-62.

Robertson P, DeCory HH, Madan A, Parkinson A. In vitro inhibition and

induction of human hepatic cytochrome P450 enzymes by modafinil. Drug

Metab Dispos 2000; 28: 664-71.

KO JW, Sukhova N, Thacker D. Chen P, Flockhart DA. Evaluation of

omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms.

Drug Metab Dispos 1997 ;25:853-62.

Hansten DD. Drug interactions of gastrointestinal drugs. In: Lewis JH, edi-

tor. A Phamacological approach to gastrointestinal disorders. Baltimore:

Williams and Wilkins, 1994: 47-74.

Yuan R, Parrnelee T. Balian JD. Upwr RS, Ajayi F, Burnett A. In vitro inter-

action studies: experience of the food and drug administration. Clin

Phamacol Ther 1999; 66: 9-15.

Kivisto KT, Kroemer HK. Use of probe drugs as predictors of drug metabo-

lism in humans. J Clin Phamacol 1997;37:40S48S:

Veshima Y. Acetaminophen metabolism in patlent with different

cytochrome P 450 2E1 genotype: Alcohol Clin Exp Res 1996; 20: 25-8.

Tanaka E, Terada M, Misawa S. Cytochrome P450 2El: its clinical and

toxicological role. J Clin Pharm Ther 2000; 25: 16575.

Novak RF. Woodcroft KJ. The alcohol-lnduclble form of cytochrome P45O

(CYP 2E1): role in toxicology and regulation of expression. Arch Pharm

R ~ s 2000; 23: 267-82.

Raucy JE. Lasker JM. Lieber CS, Black M. Acetaminophen activation by

human liver cytochrome P450 2E1 and 1A2. Arch Biochem Biophys

1989;271:270-83.

Yamazaki H. Nakano M, Giliam EM. Bell LC, Guengerich FP, Shimada T.

Requirements for cytochrome b5 in the oxidation of 7-ethoxycoumarin,

chlorroxazone, aniline, and N-nitrosodimethylamine by recombinant cyto-

chrome P450 2El and by human liver microsomes. Biochem Phannacol

1996; 52: 301 -9.

Rothman N, Smith MT, Hayes RB, Traver RD. Hoener B, Campleman S et

81,. Benzene poisoning, a risk factor for hematological malignancy, is assc-

ciated with the NQOl 609C-*T mutation and rapid fractional excretion of

chiorzoxazone. Cancer Res 1997;57:2839-42.

Peter R, Bbcker R. Beaune PH, lwasaki PH,Guengerich FP. Yang CS.

Hydroxyiation of chiotzoxazone as a specific probe for human liver cytc-

chrome P4502E1. Chem Res Toxicol 1990;3: 566-73.

Garton KJ, Yuen P, Meinwald J, Thummel KE, Kharasch ED. Stereoseiective

metabolism of enflurane by human liver cytochrome P450 2E1. D N ~ Metab

Dispos 1995;23: 1426-30.

Spracklin DK, Hankins DC, Fisher JM. Thummei KE, Kharasch ED. Cyto-

chrome P450 2E1 is the principal catalyst of human oxidative halothane

metabolism in vitro. J Pharmacol Exp Ther 1997;281:400-11.

Mraz J, Jheeta P, Gescher A, Hyiand R, Thummel K. Threadgiii MD. Inves-

tigation of the mechanistic basis of N,Ndimethyl fonnamide toxicity. Me-

tabolism of N,N-dimethyl fonnamide and its deuterated isotopomers by

cytochrome P450 2El .Chem Ras Toxicol 1993;6:107-207.

Loi CM, Day JD. Jue SO, Bush ED. Costello P, Dewey LV, ~ e s t a r k ~ . Dose-

dependent inhibition of theophyiiine metabolism by disulfiram in recover-

ing alcoholics. Clin Pharmacol Ther 1989:45:478- 88.

Raucy JL, Lasker JM. Lleber CS. Black M. Acetaminophen activation by

human llver cytochrome P 45011E1 and P 4501A2. Arch Biochem Biophys

1889; 271: 270-83.

Liaber CS. ALCOHOL: its metabolism and interaction with nutrients. Annu

Rev Nutr 2000;20: 395430.

Lieber CS. Liver diseases by alcohol and hepatitis C: early detection and

new insights in pathogenesis lead to improved treatment. Am JAddict2001;

10: 29s -50s.

Self TH, Chrisman CR. Baciewiu AM, Bronze MS. lsoniazid drug and food

interactions. Am J Med Sci 1999;317:304-11.

Guengerich FP. Kim DH, lwasaki M. Role of human cytochroma P450 2E1

in the oxidation of many low molecular weight cancer suspects. Chem Res

Toxic01 1991; 4:168-79.

Kharasch ED. Thummel KE. Mhyre J, Lillibridge J. Single dose disulfiram

inhibits chlorzoxazone metabolism: a clinical probe for P4502El. Clin

Pharmacol Ther 1993; 53: 643-50.

Higgins CF. ABC transporters: from microorganisms to man. Ann Rev Cell

Biol 1992; 8: 67-1 13.

Doige CA. Ames GFL. ATPdependant transport systems in bacteria and

humans, relevance to cystic fibrosis and mu l t id~g resistance. Ann Rev

Microbial 1993; 47: 291-319.

Schinkel AH. The physiological function of d~g-transporting P-glywpro-

teins. Semin Cancer Biol 1997; 8: 161-70.

Saitoh H, Aungst BJ. Possible involvement of multiple P-glycoprotein me-

diated efflux system in the transport of verapamll and other organic cations

across rat intestine. Pharm Res 1995; 12: 1304-10.

Cordon-Cardo C. O'Brien JP. Casals D, Rittman-Grauer L. Biedler JL,

Meiamed MR et a/.. Muitidrug resistance gene (Pglycoprotein) is expressed

by endotheliai cells at blood-brain barrier sites. Proc Natn Aced Sci USA

1989; 86: 695-8.

Axiotis CA, Guarch R. Merino MJ, Laporte N. Neumahn RD. P-g$coprotein

expression is increased in human secretary and gestational endometrium.

Lab Invest 1991; 65: 577-81.

253. Tangawara Y, Okamura N, Hirai M. Yashuhara M, Ueda K, Kioka N et a/.. Transport of digoxin by human Pgiycoprotein expressed in an procine kid- ney epithelial w i i line (LLC- PK). J Pharmac Exp Ther 1992; 263: 840-5.

254. Arias IM. Multidrug resistance genes. P-giycoprotein and the liver. Hepatology 1990; 12:159-65.

255. Ueda K. Okamura N, Hirai M, Tanigawara Y, Seaki T. Kioka N etal,. Human P-giywprotein transports cortisol, aidosterone and dexamethasone, but

not progesterone. J Biol Chem 1992; 267: 24248-52.

256. Seelig A. A general pattern for substrate recognition by P-giywprotein. Eur J Biochem 1998; 251 : 52-261.

257. Fromrn MF. P-glywprotein: a defense mechanism limiting oral bioavailabiiity and CNS accumulation of drugs. Int J Clin Pharmacol Ther 1999; 21: 69- 74.

258. Qlan XD, Beck WT. Progesterone photoaffinity labels. P-giywprotein I

multidrug resistant human leukemic lymphoblasts. JBiol Chem 1990; 265:

18753-6.

259. Genne P, Dimanche-Boitrei MT, Mauvernay RY, Gutierrez G. Duchamp 0. Petit JM et a/.. Cinchonine, a potent efflux inhibitor to circumvent

anthracydines resistance in vivo. Cancer Res 1992; 52: 2797-801.

260. Tamai I. Safa AR. Azidopine nonwmpetitively interacts with vinblastine and

cyclosporin A binding to P-giycoprotein in muitidrug resistance cells. J Biol

Chem 1991;266: 16769-600.

261. Ferry DR, Traunecker H, Kerr DJ. Clinical trials of Pgiywprotein reversal in solid tumors. EurJ Cancer 1996; 32: 1070-81.

262. Zhang X, Ritke MK, Yaiowich JC. Slovak ML, Ho JP, Collins KI et a/,. P-

glycoprotein mediates profound resistance to bisantrene. Oncol Res 1994;6:291- 301.

263. Beck WT, Cirtain MC, Glover CJ, Feisted RL, Safa AR. Effects of indoie

alkaloids on multidrug resistance and labeling of Pglycoprotein by a photoafflnity analog of vinblastine. Biochem Biophys Res Commun 1988; 153: 956-66.

Gosland MP, Lum BL, Slkic BI. Reversal by cefoperazone of resistance to

etoposide, doxorubicin and vinblastine in multidrug resistant humansarcoma

cells. Cancer Res 1989;49:6901-5.

Akiyama SI. Cornwall MM. Kuwano M. Pastan I, Gottesrnan MM. Most drug

that reverse multidrug resistance also Inhibit photoaffinity labeling of P-

glycoprotetn by a vinblastine analog. Mol Pharmacol 1988;33:144-7.

Schinkel AH, Wagenear E, Mol CAAM. P-glycoprotein In the blood brain

barrier penetration and pharmacological activity of many drugs. J Clin In-

vest 1996; 97: 2517-24.

Safa AR, Agresti M, Bryk D, Tamai I. N - ( p - A z i d ~ [ ~ ~ I ] iodophenethyl)

splperone binds to specific regions of P-glycoprotein and another rnultidrug

binding protein, spiperophilin, in man neuroblastorna cells. Biochemistry

1994; 33: 256-65.

Ford JM. Experimental reversal of P-glywprotein mediated multidrug re-

sistance by pharmacological chemosensitizer. EurJ cancer1996; 32: 991-

1001.

Germann UA. Pglywprotein mediator of multidrug resistance in tumor cells.

Eur J Cancer 1996; 32A: 927-44.

Ford JM, Prozialeck WC, Hait WN. Structural features determining activity

of phenothiazines and related drugs for inhibition of cell growth and rever-

sal of muitidrug resistance. Mol Pharmacol 1988; 35: 105-15.

Pearce HL, Safa AR, Bach NJ, Winter MA, Cirtain MC, Beck WT. Essential

features of the P-giywprotein pharmacophore as defined by a series of

reserpine analogs that modulates mu l t id~g resistance. Proc Natl Acad

Sci USA 1989: 86: 5128-32.

Thammaiah KN, Horton JK, Quian XD, Beck WT, Houghton IA, Houghton

PJ. Structural determinants of phenoxazine type compounds required to

modulate the accumulation of vinblastine and vincristine in multidrug re-

sistant cell lines. Cancer Comrnun 1990; 2: 249-59.

Nare B, Pichard RK, Georges E. Characterization of rhodamine 123 bind-

ing to Pglywprotein in human mu l t id~g resistance cells. Mol Pharmacol

1994; 45: 1145-52.

Halt WN, Gesrnonde JF, Murren JR, Yang ~ ~ ; ' C h e n H X ~ R ~ ~ S S M.

Terfenadlne (Seldane), a new drug for restoring sensitivity to multidrug

resistant cancer cells. Biochem Phamecol1993; 45: 401-6.

Mciean S, Whelan RDH, Hosking LK, Hodges OM, Thomson FH. Meyers

MB et el,. Characterizition of the Pgiycoprotein over-expression drug re-

sistance phenotype exhibited by Chlnese hamster ovary cells following

their in-vitro exposure to fractionated X-irradiation. Biochem Biophys Acta

1993; 1177: 117- 126.

Uchshmi T. Kohno K, Tanimura H, Matuso K, Sato S. Uchida Ye t a/,. En-

hanced expression of the human mu l t id~g resistance 1 gene in response

to UV light irradiation. Cell Growth Differ 1993; 4: 147-57.

Chin KV, Tanaka S, Dariington G, Pastan I, Gottesman M. Heat shock and

arsenate increase expression of mu l t id~g resistance (MDRI) gene in hu-

man renal carcinoma cells. J Biol Chem 1990; 265: 221-6.

Scheutz EG, Beck WT. Schuetz JD. Modulators and substrates of P-giyco-

protein and cytochrome P 450 3A coordinately regulates these proteins in

human colon carcinoma cells. Mol Pharmacol 1995; 49: 31 1-8.

Kajiji S, Dreslin JA. Griuuti K, Gros P. Structural distinct MDR modulators

show specific patterns of reversal agents P-glycoprotein bearing unique

mutations at Serine. Biochemistry 1994; 33: 5041-8.

Boliag DM, McQueney PA, Zhu J. Hensens 0, Koupal L, Liesch J et al,.

Epothiiones, a new class of microtubules stabilizing agents with a taxol like

mechanism of action. Cancer Res 1995; 55: 2325-33.

Tsuwo T, lida H, Tsukagoshi S. Sakurai Y. Overcoming vincristine resis-

tance in P388 leukemia in vivo and in vitro trough enhanced cytotoxicity of

vincristine and vinblastine by verapamil. Cencer Res 1981; 41: 1967-72.

Wishart GC. Bisset D, Paul J, Jodreli D, Harnett A, Habeshaw T et al..

Quinidine as a resistance modulator of eporubicin in advanced breast can-

cer: mature results of a placebo- controlled randomized trail. J Clin Oncol

1994; 12: 1771-7.

Pineda HM, G iawne G. Pgiycoprotein - A marker of cancer cell behaviour.

N Engl J Med 1995; 333: 141 7-9.

Yuen AR. Slkic BI. Multidrug resistance in lymphoma. J Clin Oncol 1994;

12: 2453-9.

Twentyman PR, Bieehen NM. Resistance modification by PSC-833, a novel

non-Immunosuppressive cydosporin A. Eur J Cancer 1991; 27: 1639-42.

lo4

Mayer U. Wagenaar E, Beijnen JH, Smit JW, Meijer DKF, Asperen JV et

el.. Substantial excreiion of digoxin via the intestinal mucosa and preven-

tion of long term digoxin accumulation in the brain by the mdrla Pglyco-

protein. Br J Phamecol1996; 119: 1038-44.

Charman WN, Porter CJ. Mithani S. Dressman JB. Physiochemical and

physiological mechanisms for the effects of food on drug absorption: the

roie of lipids and pH. J P h a n Sci 1997; 86: 269-82.

Doherty MM, Pang KS. First-pass effect: significance of the intestine for

absorption and metabolism. Drug Chem Toxic01 1997; 20: 329-44.

Fieisher D. Li C, Zhou Y, Pao LH, Karim A. Drug, meal and formulation

interactions influencing drug absorption after oral administration. Clinical

implications. Clin Phannacokinet 1999; 36: 233-54.

Mountfield RJ. Senepin S, Schieimer M, Walter I, Bittner B. Potential inhibi-

tory effects of formulation ingredients on intestinal cytochrome P450. Int J

Pham 2000;211: 89-92.

Horter D, Dressman JB. Influence of physicochemical properties on disso-

lution of drugs in the gastrointestinal tract. Adv Drug DeQv Rev 2001; 46:

75-87.

Hathcock JN. Metabolic mechanisms of drug-nutrient interactions. Fed Proc

1985;44:124-9.

Van de Waterbeemd H, Smith DA. Jones BC. Lipophilicity in PK design:

methyl. ethyl. futile. J Comput Aided Mol Des 2001; 15: 273-86.

Khanna JM, Chung S. Ho G, Shah G. Acute metabolic interaction of etha-

nol and drugs. C u r Alcohol 1979;7:93-108.

Jung T. Kamm W. Breitenbach A, Kaiserling E, Xiao JX, Kissel T. Biode-

gradable nanoparticles for oral delivery of peptides: Is there a roie for poly-

mers to affect mucosal uptake? Eur J Pham Biophenn 2000; 50: 147-60.

Nolting A, Sista S, Abramowitz W. Single-dose study to compare the phar-

macokinetics of HFA flunisolide and CFC flunisolide. J Phann Sci 2002

;Dl :424-32.

Janknegt R, de Marie S. Bakker-Woudenberg IA, Cromme!in DJ. L i p w -

rnal and lipld formulations of amphotericin 8. Clinical pharmamkinetics.

Clin Phannacokinet 1992; 23: 279-91.

Sapentein S, Edgren RA, Jung D, Mroszczak EJ, Lee GJ, Dorr A, et a/,.

Phanacokinetics of norethindrone: effect of parUcle size. Contraception 1989 ;40:731-40.

Strother A. The influence of high sugar consumption by mice on the dura-

tion of action of barbiturates and in vitro metabolism of barbiturates, aniline and p-nitroanisole. J Phannacol Exp Ther 1971; 179: 490-8.

Naim HY. Molecular and cellular aspects and regulation of intestinal lac- tose- phlorizin hydrolase. Hlstol Histopathol2001; 16: 55341.

Fleisher D, Lippert CL. Sheth N et a/.. Nutrient effect in intestinal drug ab-

sorption. J Controlled Release 1990;l I : 41-9.

Carver PL, Fleisher D, Zhou SY et at,. Meal composition effects on the oral

absorption of indinavir in HIV- infection patients. Phann Res 1999; 16:

718-24.

Miles C. Dickson P, Rana K et el,. CCK antagonist pre-treatment inhibits meal-enhanced drug absorption in dogs. Regd Pept 1997; 68: 9-14.

Vessal M, Choun MO, Bissell MJ. Bissell DM. F~c toSe utilization and

altered cytochrome P 450 in cultured hepatocytes from adult rats. Biochimica

et Biophysica Acta 1980; 633: 201 -10.

Bissel DM. Gene expression and caminogenesis. In: New York: Academic

press, 1975: 11 9-36.

Guzelian P. Effect of carbohydrates on cytochrome P 450. Fed Proc 1974;

33: 545-51.

Chow HH, Levin RJ. Pharmacokinetiw of D-propranolol following oral, in-

tra-arterial and intraportal administration: contrasting effects of oral glu- cose pretreatment. Biophann Drug Dispos 1093; 14: 217-31.

Oshida Y, Tachi Y, Morishita Y, Kitakoshi K, Fuku N, Han YQ, Ohsawa I,

Sato Y. Nitric oxide decreases insulin resistance induced by high-fructose

feeding. Horn Matab Res 2000 ;32:339-42.

Stewart CC. Strother A. Glucose consumption by rats decreases cytochrome

P 450 enzyme activity by altering hepatic lipids. Llfe Sci 1999; 64: 2163-

72.

Lopez-Garcia MP. Endogenous nitric oxide is resporhible for a h a r t y loss of P450 in cultured rat hepatocytes. FEES Lett 1998;438:145-9.

Djordjevic D, Nikoiic J, Stefanovic V. Ethanol interactions with other cyto-

chrome P450 substrates including drugs, xenobiotics, and carcinogens.

Pathoi Biol (Paris) 1998; 46:760-70.

Jorquera F, Culebras JM, Gonzaiez-Gailego J. Influence of nutrition on

liver oxidatlve metabolism. Nutrition 1996;12:442-7.

Wade AE. Effects of dietary fat on dmg metabolism. J Environ Pathol Toxicoi

Oncol 1986; 6:161-89.

Anderson KE. Influences of diet and nutrition on clinical pharmacokinetics.

Clin Pharmacokinet 1988;14:325-46.

Hathcock JN. Metabolic mechanisms of drug-nutrient interactions. FedProc

1985;44:124-9.

Waiter-Sack I. Klotz U. Influence of diet and nutritional status on drug me-

tabolism. Clin Phamacokinat 1996;31:47-64.

Chapman A, Keane PE. Commission on classification and terminology of the international league against Epilepsy. Proposal for revised classifica- tion of epilepsies and epileptic syndromes: Epilepsia ; 1989: 30: 389-99.

McNamara JO. Drugs Effective in the therapy of the epilepsies, In Hardrnan JG and Limbird LE (eds), Goodman and Gilman's. The Pharmacological basis of therapeutics: New York, McGraw Hill, 2002, 5334.

Maas 8. Garnett WR. Pellock JM, Comstock TJ. A comparative bioavailability

study of carbamazepine tablets and a chewable tablet formulation. Ther

Drug Monit 1987;9:28-33.

Mesdjian E. Seree E. C h a ~ e t 8. Mirrione A, Bourgarel-Rey V, Desobry A,

Barra Metabolism of carbamazepine by CYP3A6: a model for in vtro drug

interactions studies. Life Sci 1999; 64: 827-35.

Weber A. Kaplan M, Chughtai SA, Cohn LA, Smith AL, Unadakt JD. CYP3A

inductive potential of the rifamycins, rifabutin and rifampin, in the

rabbit.Biopham Drug Dispos 2001 ;22:157-63.

Beliucci G, Berti G, Chiappe C . Carbamazepine: J Med Chem 1987;30:

768-72.

Maggs JL, Pirmohamed M, Kitteringham NR. Park BK. Characterization of

the metabolites of carbamazeplne in patient urine by liquid chrornatogra-

phylmass spectrometry. Dwg Metab Dispos 1997 ;25:275-80.*

Karunanayake EH. Joice PD, Peiris JB, Meijer JW, Meinardi H. Serum pro-

tein binding of antiepilepticdrugs In Srl Lankans. Ceylon Med J 1990;35:25

8.

Niemi M, Backman JT, Neuvonen M. Neuvonen PJ. Kivisto KT . Rifampin

decreases the plasma concentrations and effects of repaglinide: Clin Phamacol Ther 2000: 68: 495- 500.

Baker AF, Dorr RT. Drug interactions with the docetaxei: clinical implica-

tions: Cancer Treat Rev 2001; 27: 221-233.

Robertson RM. Robertson D, 1996, Drugs used for the treatment of Myo-

cardial Ischemia. In Hardman JG and Limbird LE (eds), Goodmen and

Gilrnan's. The Pharmacological basis of therapeutics: New York. McGraw

Hill, 759-779.

Kaplinsky E. Managment of angina pectoris. Modem concepts: Drugs 1992;

43: 9s-14s.

Opie LH. Calcium channel antagonists: Part VI: Clinical pharmacokinetics

of first and second-generation agents. Cardiovasc Drugs Ther 1989;3:482-

97.

Saenz-Campos D, Bayes MC. Maltin S, Barbanoj MJ. Jane F. Gender re-

lated pharmacokinetics of diitiazem in healthy subjects, lnt J Clin Phamacol

Ther 1995; 33: 397-400.

Hung J, Hackett PL, Gordon SP, Ilett KF. Pharmacokinetics of diltiazem in

patients with unstable angina pectoris. Clin Pharmacol Ther 1988; 43:466-

70.

Belpaire FM, Bogaert MG. Binding of diltiazem to albumin, alpha 1-acid

glycoprotein and to serum in man. J Clin Pharmecol 1990;30:311-7.

Chaffman M, Brogden RN. Diltiazem: A review of its pharmacological

properties and therapeutic efficacy: Drugs 1985;29: 387-92.

Cowlas GH. Cardiovascular agents, In Delgado JN and Remers WA (eds),

Wilson end Gisvold's Textbood of ofgenic medicinal and pharmaceutical

chemistry: Philadelphia. J.B. Lippincon company 1991; 535-83.

Sutton D . Alison M. Butler, Nadln L, Murray . Role of CYP3A4 in Human

Hepatic Diltiazem N-Demethylation: Inhibition of CYP3A4 Act iW by Oxi-

dized Diltiazem. Metabolites 1897; 282:294-300.

Lambrecht RW, Gildemeister OS, Williams A, Pepe JA, Tortorelli KD,

Bonkovsky HL. Effects of selected antihypertensives and analgesics on

hepatic porphyrin accumuiatlon:lrnplications for clinical porphyria. Biochem

Pharmacol 1999 ;58:887-96.

Bleck JS. Thiesemann C, Kliem V, Christians U, Hecker H, Repp H eta/,.

Diltiazem increases blood concentrations of cyclized cyclosporine metabo-

lites resulting in different cyclosporine metabolite patterns in stable male

and female renal allograft recipients. Br J Clin Phermecoll996; 41:551-6.

Marumo H, Satoh K, Yamamoto A. Kaneta S, ichihara K. Simvastatin and

atorvastatin enhance hypotensive effect of diltiazem in rats: Yakugaku

Zasshi 2001; 121: 7614

Norlin A, Lu LN, Guggino SE, Matthay MA, Folkesson HG. Contribution of

amiloride-insensitive pathways to alveolar fluid clearance in adult rats. J

Appl Physiol2001;90:1489-96.

Pucilowski 0 , Rezvani AH, Overstreet DH, Janowsky DS. Calcium channel

inhibitors attenuate consumption of ethanol, sucrose and saccharin solu-

tions in rats. Behav Pharmacol 1994;5:494-501.

Azie NE, Brater DC, Becker PA. Jones DR. Hall SD. The interaction of

diltiazem with iovastatin and pravastatin. Clin Pharmacol Ther 1998;64:369-

77.

lsaacson El. Central nervous system depressants, In Delgado JN and

Remers WA (eds), Wilson and Gisvold's Textbook of organic medicinal

and pharmaceutical chemist~: Philaelphia, J.B Lippincon company

1991;359410.

Hardman JG. Limbird LE (eds) Goodman and Gilman's The pharmacologi-

cal basis of therapeutics. loh edition. New York: McGraw-Hill. 2001; 528-

531.

Doak KK, Haas CE, Dunnigan KJ. Reiss RA. Reiser JR, Huntress J. Altaveia

JL. Bioavailabiiity of phenytoin acid and phenytoin sodium with enteral

feedings. Phannacotherapy 1998;18:63745.

livanalnen M. Phenytoin: effective but insidious therapy for epllepsy in people

with intellectual disability. J Intellect DlsabN Res 1998;42:24-31.

Glancarlo OM. Venkatakrishnan K, Granda BW. Van Moltke LL. Greenblatt

DJ, Relative contributions of CYPZCB and C l 0 to phenytoin 4-hydroxyla-

tion in vitro Inhibition by sulfaphenazole, omeprazole. Eur J Clin Phannacol 2001; 57: 31-6. .

Tanaka E. Clinical importance of nongenetic and genetic cytochrome P450

function tests in liver disease. J Clin Phann Ther IQ98;23:161-70.

Kerb R, Aynaciogiu A S. Brockmoller J, Schlagenhaufer R, Bauer S, zekeres

T, etai,. The predictive value of MDRI, CYP2C9, and CYP2C19 poiymor- phisms for phenytoin plasma levels. Phannacogenomics 2001;1:204-10.

Liu H. Delgado MR Interactions of phenobarbital and phenytoln with carbamazepine and Its metabolites' concentrations, concentration ratios,

and leveildose ratios in epileptic children. Epilepsia 1995;38:249-54.

Sandor P, Sellers EM. Dumbrell M, Khouw V.Effect of short- and long-term

alcohol use on phenytoin kinetics in chronic alcoholics. Clin Pharmacol Ther 1981;30:390-7.

lyer KS, Thampuran RV.lnteractions between reserpine and anticonvulsants

on convulsion parameters. Indian J Physiol Phannacol 1978;22:372-7.

Malli R, Jones WN, Rindone JP. Labadie EL.The effect of sucraifate on the

steady-state serum concentrations of phenytoin. Drug Metabol Drug Inter-

act 1989;7:287-93.

Krasinski K. Kusmiesz H. Nelson JD. Pharmacoiogic interactions among chloramphenicol, phenytoin and phenobarbital. Padiatr Infect Dis 1982

;1:232-5.

Hansen JM, Kristensen M, Skovsted L. Christensen LK. Dicoumarol-induced

diphenyihydantoin intoxication. The Lancet 1966;2:2656.

Svendsen TL, Kristensen MB. Hansen JM, Skovsted L. The influence of

disulfiram on the half life and metabolic clearance rate of diphenylhydan-

toln and toibtamide in man. Eur J Clin Phannacol 1976;09:439-41.

Yew WW, Lau KS. Ling MH. Phenytoln toxicity in a patient with isoniazid-

induced hepatitis. Tubercle 1991;72:309-10.

Rafi JA. Frazier LM, Driscoll-Bannister SM, O'Hara KA, Gamett WR, Pugh

CB. Effect of over-the-wunter cimetidlne on phenytoin concentrations In

patients with seizures. Ann Phannacother 1999;33:789-74.

Nelson MH. Blrnbaum AK, Remmel RP. Inhibition o f phenytoin Hydroxyla- tion in human liver microsomes by several selective serotonin re-uptake inhlblton: Epilepsy Res 2001; 44: 71-82.

110

Robert JL, Morrow JD. Analgesic-Antipyretic and Antllnffammatory agents

and drugs employedln the treatment of Gout. In Hardman JG and Llmbird

LE (ads), Goodman end Giimank. The Phamecologicei basis of thera- peutics: New York, McGraw Hill 2002; 703-5.

Willette RE. Analgesic Agents, in Delgado JN and Remers WA (eds), Wilson and Glsvoidk Textbook of orgenlc medicinal and pharmaceutical chemistw Philadelphia, J.B. Lippinwtt company 1991; 629-73.

lshikawa T, Koizumi N, Mukai B. Utoguchi N, Fujli M, Matsumoto M et el..

Phanacokinetics of acetaminophen from rapidly disintegrating compressed tablet prepared using microcrystalline cellulose (pH-M-06) and spherical sugar granules. Chem Pharm Bull (Tokyo) 2001;49:230-2.

Milligan TP, Morris HC. Hammond PM. Price CP. Studies on paracetamol binding to serum proteins. Ann Clin Biochem 1994;31:492-6.

Tran A, Treluyer JM, Rey E, Barbet J, Ferracci G, d'Athis P, Vincent J, Pons G. Protective effect of stiripentol on acetaminophen-induced hepatotoxic-

ity in rat. Toxic01 Appl Phemecol 2001;170:145-52.

Veshima Y. Acetaminophen metabolism in patient with different cytochrome P 450 2El genotype: Alcohol Clin Exp Res 1996; 20: 25-8.

Abramson SR, weissmann G. The mechanism of action of non-steroidal

anti-inflammatory drugs: Arthritis Rheum 1989 ; 32: 1-9.

Oforah E, Anyogo S. The contributions of various chloroquine salts to the

biiiary and urinary excretion of hepatic paracetamol conjugation metabo-

lites in the rat. Drug Metaboi Drug Interact 2000;16:129-41.

Poulsen HE, Ranek L, Jorgensen L. The influence of disulfiram on ac-

etaminophen metabolism in man. Xenobiotica 1991;21:243-9.

Lee SM, Cho TS, Kim DJ, Cha YN. Protective effect of ethanol against

acetaminophen-induced hepatotoxicity in mice: role of NADH:quinone re-

ductase. Biochem Pharmecol 1999;58: 1547-55.

Zand R, Nelson SD, Slattery JT, Thummel KE. Kalhorn TF. Adams SP,

Wright JM. Inhibition and induction of cytochroma P4502E1-catalyzed oxi- dation by isoniazid in humans. Clin Phennecol Ther 1993;54:142-9.

Tatro SD. Drug interaction facts. St Louis, Missouri: JB L i p p i n w e , 1998

5-9.

Smith TW. Kelly RA. Stevenson LW, Braunwald E. Management of heart

failure. In, Heart Disease. Braunwald E editor- Saunders. Philadelphia 1997, 492-514.

Roden DM. Antiarrhythmic drugs. In Goodman and Gilman's The Pharma-

cological basis of therapeutics. Hardman JG, Limblrd LE. McGraw-Hill. New York 2001, 958-9.

Antolovic R. Kost H, Mohadjerani M, Linder D. Linder M. Schonar W. A specific binding protein for cardiac glywsides exists In bovine serum. J

Biol Chem 1998 ;273 (26): 16259-64.

Seeling A. A general pattern for substrate recognition by P-glywprotein. Eur J Biochem 1998;251:252-61.

Schinkel AH, Wagenaar E, Deernter LV. Mol C U M , Borst P. Absence of

the m l a P- glywprotein in mice affects tissue distribution and pharmawki- netics of dexamethasone, digoxin and cyciosporin A. J Clin lnves 1995;96: 1698-1 705.

Gan F, ishii A, Seno H, Watanabe-Suzukl K, Kumazawa T, Suzuki 0.

Identification and quantification of cardiac glycosides in blood and urine

samples by HPLCIMSIMS. Anel Chem 1999;71:4034-43.

Wojcicki M, Dmzdzik M, Sulikowskl 6. Gawronska SJ, Wojdcki L, Rozewicka,

et a/.. Pharmawkinetic of intragastrically administered digoxin in rabbits

with experimental bile duct obstnrctlon. J Pharm Pharmacol1997;49:1082-

5.

Tse HF, Lam YM, Lau CP. Cheung EM, Kumana CR. Comparison of digoxin

Venus low- dose amiodarone for ventricular rate control in patients with

chronic atrial fibrillation. Clin Exp Pharmacol Physiol2001;28:446-50.

Okamura N. Hiral M, Tanigawara Y, Tanaka K, Yasuhara M, Ueda K, Komano

T, Hori R. Digoxin-cyclosporin A interaction: modulation of the multidrug

transporter P-glycoprotein in the kidney. J Pharmacol Exp Ther

1993;266:1614-9.

WakasugiH, lshizuka R, Koreeda N, Yano I. Futami 1. Nohara R. Sasayama

S, lnui K. Effect of ltraconazole on digoxin clearance In patients with wn-

gestive heart failure. Yakugaku Zasshi 2000;120:807-11.

Kofinas AD, Simon NV, Sagei H, Lyttle E. Smith N, king K. Treatment of fetal supraventricular tachycardia with flecainide acetate after digoxin

failure. Am J Obstet Gynecol1991;165:630-1.

Lee G. Schlichter L, Bendayan M. Bendayan R. Functional expression of

P-glywprotein in rat brain microglia. J Pharmacol Exp Ther 2001;299:204-

12.

Pauli-Magnus C, Rekersbrink S. Klotz U. Fromm MF, Interaction of

omeprazole, lansoprazole and pantoprazoie with P-glycoprotein. Naunyn

Schmiedebergs Arch Pharmacol200 1 :364:551-7.

Perloff MD, von Moltke LL, Stormer E. Shader RI. Greenblatt DJ. Saint

John's wort: an in vitm analysis of P-glywprotein induction due to extended

exposure. Br J Pharmacol2001 ;134:1601-8.

Ali MAT, Al Swayeh OA. Natural honey prevents ethanol-induced increased

vascular permeability changes in the rat stomach. J Ethenophamacoll997;

55: 231-7.

Cooper RA. Molan P, Harding. Antibacterial activity of honey against strains

of staphylococcus aureus from infected wounds. J R Soc Med 1999; 92:

283-5.

Macht Dl. Barbara-Gose J. Evaluation of drugs on gastrointestinal motility.

J Am Pharm Asso 1931 ; 20: 558-61.

Garg SK, Isiam AFM , Kumar N. Effect of septilin - A herbal preparation on

pharmawkinetic of carbamazepine in rabbits. Indian J Physiol Pharmacol

1998; 42: 527-30.

Gerson 8. Bell F, Chan S. Antiepileptic agents- primidone, phenobarbital,

phenytoin and carbamazepine by reversed phase liquid chromatography.

Clin Chem 1964; 30: 105-7.

Yeunk PK, Mosher SJ , Pollack PT. Pharmawkinetics and metabolism of

diltiazem in rabbits after a single intravenous or single oral administration.

Eur J Drug Metab Pharmacokinet 1991; 16: 69-74.

Chaudhary RS, Gangwal SS, Avachat MK, Shah YN, Jindal KC. Deteni-

nation of diltiazem hydrochloride In human serum by high-performance

liquid chromatography. J Chromatography 1993; 614: 261-5.

Rustum AM. Determination of Dlltiazem in human whole b lwd and plasma

by high performance liquid chromatography using a'po~ymeric%vened-

phase column and utilizing a saltlngout extraction procedure. J Chmma-

togrephy 1989; 490: 385-71.

113

Drozdzik M, ~awronska-Szklarz 8, Wojclcki J. The pharmacokinetia of

phenytoin in rabbits with hyperlipidemia Induced by high fat diet. Acta Pol

Pharm 1994; 51: 517-23.

Kwaiatkowski A, Gawronska-Szklarz 8, Drozdzik M, Wojcicki J. Phanna-

cokinetic of paracetamol after removal of ovaries in rabbits. Endokrynol

Pol 1993; 44: 73-6.

Malan J. Chronopharmacokinetics of paracetamol in normal subjects. Br J

Clin Pharmacol 1985; 19: 843-5.

Brustolin D. Sirtoii M, Tarenghi G. An enzyme-labeled imrnunometric assay

for quantitation of digoxin in serum or plasma. Ther Dnrg Monit 1992;14:72-

7.

Watanabe J, Mondo H, Takamori Y, Takeda K. Kanamura S. Effect of

phenobarbitol on intralobular expression of CYP2Bll2 in livers of rats: dif-

ference in the expression between single and repetitive administrations.

Biochem Pharmacol 2000; 60:285-92.

iba MM. Scholi H. Fung J. Thomas PE. Alam J, lnduction of pulmonary

CYPlAl by nicotine. Xenobiotlca 1998;28 : 827 - 32.

Wong A, Bandiera SM, lnduction of hepatic cytochrome P450 28 and P450

3A isoenzymes in rats by zoiazepam, a constituent of Teiazol. Biochem

Pharmacol 1998;55 :201 - 12.

Kim SK. Kim YC, Effect of a single administration of benzene, toluene or

m-xyiene on carboxyhaernogiobin elevation and metabolism of

dichloromethane in rats. J Appl Toxic01 1996;16 : 437 - 40.

Reppas C, Eleftheriou G, Macharas P et el. Impact of elevated viscosity in

the upper gastrointestinal tract on drug absorption in dogs. Eur J Pharm

Sci 1998; 6 :I31 - 36.

Roa RP and Diwan PV. Comparative in-vivo evaluation of diltiazem

hydrochloride following oral and transdermal administration in rabbits. Ind

J Phamacology 1999; 31 : 294 - 98.

Nakamura 1, Okada K. Nagata K, Yamazoe Y. Intestinal cytochmme P 450

and response to rifampicin in rabblts. Jpn J Phamawl2000; 82;332 - 39.

Sukrltl, Garg SK. lnfluenoe of honey qn the phannacokinetics of phenytoin

h rabblts. Proceedings of the 34" Annual wnference of the Indian phar-

macolqicai society [ACIPS]; 2002 Jan 10-12: Nagpur, India. 2002, p.27.

114

Tables

I . Substrate, inducers and inhibitors of cytochrome P 450 3A4 enzyme. 2. Substrate, inducers and inhibitors of cytochrome P 450 2C19 en-

zyme. 3. Substrate, inducers and inhibitors of cytochrome P 450 2E1 enzyme. 4. Substrate, inducers and inhibitors of Pglycoprotein. 5. Effect of honey on pharmacokinetic parameters of carbamazepine

(CBZ). 6. Effect of artificial honey (Art.H) on pharmacokinetic parameter of

carbamazepine (CBZ). 7. Effect of honey on pharmacokinetic parameters of orally administered

diltiazem (DTZ). 8. Effect of honey on pharmacokinetic parameters of intravenously ad-

ministered diltiazem (DTZ). 9. Effect of honey on pharrnacokinetic parameters of phenytoin (DPH). 10. Effect of honey on pharrnacokinetic parameters of orally administered

paracetamol (PRL). 11. Influence of honey on gastric motility (Charcoal meal test in mice). 12. Effect of honey on pharmacokinetic parameters of Digoxin

Figures 00264C

1. Effect of honey (Hn) on plasma concentration of carbamazepine (CBZ).

2. Effect of artificial honey (Art.H) on the plasma concentration of carbamazepine (Carb).

3. Effect of single (S.D) and multiple (M.D) dose of honey (Hn) on the mean plasma concentration of orally administered diltiazem (DTZ).

4. Effectof multiple dose (M.D) of honey (Hn) on the mean plasma concentration of intravenously administered diltiazem (DTZ).

5. Effect of honey (Hn) on plasma concentration of phenytoin (DPH). 6. Effect of honey (Hn) on the mean plasma con~entrationi8f orally

administered paracetamol (PRL). 7. Effect of honey (Hn) on plasma concentration of digoxln (DIG).