AllGO AGA ABSTRACTS

5339

GASTRIC EMPTYING OF INDIGESTIBLE TABLETS IN RELA·TION TO THE MIGRATING MOTOR COMPLEX (MMC).Darius Apel, Baerbel Ueberschaer, Klaus Ewe, Clin Ludwigshafen, Lud­wigshafen, Germany; Univ Mainz, Mainz, Germany.

Indigestible tablets leave the stomach during phase III of the MMC. Theaim of the study was to measure the MMC manometrically and to dem­onstrate the gastric emptying by means of the enteric-coated tablet and ofa metal detector. Material and methods: 20 (m/f= Ill) healthy volunteersaged 22-62 yr were investigated. The manometric probe included 8 side­holes and I central channel with the distal end connected to a latex ballooncontaining water for sonographic localization of the probe. For the mea­surement of gastric emptying we used the metal detector and a metal coretablet (6 mm in size). The position of tablet was documented in a systemof coordination with the navel as the central point. The most importantcharacteristics for gastric emptying of the tablet were a rapid movementover a distance of 6-10 em from the left of midline to the right as well asa decrease in intensity because of the retroperitonel localization and thechanging location in the lower abdomen. After an overnight fast of at least12 h the subjects ingested 100 ml of a liquid meal (420 kJ) with the tablet.Than the manometric probe was brought into position. Results: The tableshows the gastric emptying of the indigestible particle in relation to thephases of the MMC. In one subject the tablet did not empty during the firstMMC at all but during the phase III of the following MMC. The mediantime of gastric emptying of the tablet after the ingestion of a liquid mealwas 150.0 [range 80-260] min. Discussion: The indigestible tablets emptythe stomach not only during the phase III of the MMC as it was assumedtill now. The gastric emptying of an acid resistent particle can occur inapproximately 35% during the phase II of the MMC. One possible expla­nation for that could be the gaping pylorus. Whether this phenomenon waspresent in the study individuals with the emptying of the table during thephase II could not be anserwed by the design of this investigation.

GASTROENTEROLOGY Vol. 118, No.4

5341

A FOUR COMPONENT MODEL CAN QUANTITATIVELY PRO·FILE GASTRIC EMPTYING IN DIABETIC GASTROPATHY.Naeem Aslam, Hani M. Rashed, Jide Familoni, Thomas L. Abell, Univ ofTennessee, Dept of Medicine, Memphis, TN; UT Bowld Hosp Univ ofTennessee, Memphis, Memphis, TN; Univ of Memphis, Memphis, TN;Univ of Tennessee-Memphis, Memphis, TN.

Introduction. In diabetes mellitus(DM), abnormalities of Autonomic Func­tion Testing (AFT) and Electrogastrography (EGG) are well documented.We have previously noted that Delayed and Very Delayed Gastric Emp­tying (GET) can be predicted by adrenergic and cholinergic AFT. Inaddition patients with very rapid GET can be predicted by AFT, EGG andGlycohemoglobin values (GE.110(4): A 35,1996). We investigated thehypothesis that GET in patients (pts) with diabetic gastropathy can bequantitatively profiled by a four component model, using Adrenergic,Cholinergic, Enteric, and Metabolic parameters. Methods. We analyzed 76patients with DM presenting with signs and symptoms of Diabetic gas­tropathy (nausea, vomiting, early satiety, anorexia, bloating, and/or abdom­inal pain). Adrenergic autonomic tests were by vasoconstriction to cold(YC). Cholinergic AFT was measured by EKG R to R Interval (RRI). TheEnteric Nervous System was measured by cutaneous electrogastrography(EGG). The Metabolic parameter Glycosylated hemoglobin (GH) wasmeasured by radioenzymatic assay. Solid GET was by T 50 as: very rapid(VR), rapid (R), normal(N), delayed (D), or very delayed (YD). Results.The data, including comparisons by ANOV A, is summarized in the tablebelow. VC is lowest in the VD group, and increases linearly with gastricemptying ( r= 0.99, p<O.01). RRI is also lowest in VD group, andincreases with gastric emptying. (r= 0.83, p=0.(8); EGG also tends toincrease with gastric emptying (r=-0.8, p=0.09). GH is lowest in the Ngroup but did not change in a linear manner. Conclusion. A four compo­nent model can quantitatively profile gastric emptying in patients withsigns and symptoms of Diabetic Gastropathy.

Gastric emptying 95%·confidence int.

MUltiple-dose pharmacokinetics oftegaserod (mean ± SD and median for1m,,)

5340

SIMILAR PHARMACOKINETICS OF TEGASEROD (HTF 919) INPATIENTS WITH CONSTIPATION· AND DIARRHEA·PREDOM·INANT IRRITABLE BOWEL SYNDROME.Silke Appel-Dingemanse, James Rawls, Joan Heggland, Joelle Campes­trini, Romain Sechaud, Novartis Pharmaceuticals, Basel, Switzerland; No­vartis Pharmaceuticals, East Hanover, NJ; Novartis Pharmaceuticals, RueilMalmaison, France.

Background: Tegaserod (T,HTF 919) is a selective partial agonist at the5-HT4 receptor. T belongs to a new class of agents in development for thetreatment of functional motility disorders of the gastrointestinal (GI) tract.In cI inical studies T has been shown to be effective and well tolerated in thetreatment of IBS. Objective: Assessment of T pharmacokinetics (PK) inpatients with constipation-predominant irritable bowel syndrome (C-IBS)and diarrhea-predominant IBS (D-IBS). Methods: The PK of T werecharacterized after 2 and 6 mg b.i.d. administrations for 4 weeks. Evalu­ations were performed in 54 C-IBS patients in a Phase III efficacy studyand in 32 D-IBS patients in a Phase II safety study. Patients were instructedto take the drug within 30 minutes prior to a meal. Results: The table belowdisplays the PK results of T for 6 mg b.i.d., the recommended therapeuticdosing regimen in C-IBS, together with those from patients with D-IBS andfasting healthy subjects (HS, study on dose proportional PK). AUC, andCn" " . " of T were similar between patients with C-IBS and D-IBS. Similarresults were obtained for the 2 mg b.i.d. dosing regimen. To compare themultiple-dose PK of T between patients with IBS and HS (fasted admin­istration) food effect must be taken into account. When administered withfood, the systemic exposure of T was reduced by 40-65 % and themaximum plasma concentration by 20-40 %. Multiple-dose PK of T werecomparable among IBS patients and HS when considering the food effect.Time to Cm"x was about I h after drug intake in all three populations.Conclusions: The PK of T are similar in patients with C-IBS and D-IBSindicating that the type of bowel function abnormality has no major impacton the PK of T. The PK of T were also comparable between IBS patientsand HS.

aT intake prior toa meai, bfasted T intake

Phase IPhase IIPhase III

noemptying duringl.MMC

1m"." (h)Cm"."(nglmL)AUC, (h'ng/mL)

7 (35%)12(60%)

1(5%)

C·IBS patients'n=32

1.01.7±0.75.7 ± 2.5

D·IBS patients'n=16

1.01.9±1448± 24

154-59.2 %36.1-80.9 %

0.1-24.9 %

Healthy subjects'n=18

0.82.7± 1.28.9 ± 4.2

GET T50 Solid VC RRI EGG GH

VDelayed n=23 240±0· 41±6' 59±1.8 31±0.1 754±0.56Delayed n=15 183.4±4.6. 54±7.4 10412 3.47±0.09 719±0.4Normal n=15 1381±25' 60±6.8 15.3±307 322±01 669±033Rapid n=7 111.7±018 63.9±75 1234±3.4 3.43±0 17 737±102VRapid n=16 77.1±5.5' 65.8±5.97' 17.4±36 365±022 792±035All patients Linear Reg. r=-0.99 r=-083 r=-0.8 r=-0.15

p<0.01 p=0.08 p=0.095 p=0.8

·p<0.05 byANOVA

5342

DOES AGING AFFECT GASTRIC MYOELECTRICAL ACTIVITYIN PATIENTS WITH FUNCTIONAL DYSPEPSIA?Bashar M. Attar, Melchor Demetria, Srikiran Pothamsetty, Philip E.Donahue, Jiande Chen, Cook County Hosp, Chicago, IL; Univ of TexasMed Branch, Galveston, TX.

Gastric dysrhythmia has been associated with functional dyspepsia. Gastricmyoelectrical activity (GMA) is absent at birth, develops following theneonatal period and is similar in healthy children and adults. The aim of thestudy was to investigate the effect of age on gastric myoelectrical activityin patients with functional dyspepsia. Methods: We studied the gastricmyoelectrical activity in 68 patients (40F, 28M), mean age 46 years (rangeof 21-78 years). Electrogastrography (EGG) was performed one hour priorto and one hour after a standard meal (turkey sandwich, 500 cal). Com­puterized spectral analysis (Polygram, Synectics) was utilized to compute:I) the number and percentage of normal slow waves (normal 2.4-3.6 cpm,bradygastria <2.4, tachygastria 3.7-9; a value below 60% was defined asabnormal); II) the ratio of pre-prandial and post-prandial EGG dominantpower: III) the minute to minute variation of the dominant frequency(DFIC) and power (DPIC). To investigate the correlation between gastricmyoelectrical activity and age, patients were divided into Group I: 2:50years (n=40), and Group II: age <50 years (n=28). Results: The rhyth­micity of the slow waves was abnormal in both groups in the fasting state(54% vs 74%) and in the fed state (540/c vs 22%). The older (Group I)patients had significantly lower prevalence of tachygastrialtachyarrhythmia(>4% in the fasting or fed recording) than in younger (Group II) patients(11.5% vs 46.7%, p=0.025) in the fasting state. This difference was,however, not significant in the fed state (30.1 % vs 42.9%, p=0.5l. Theunderlying mechanism is not known but a similar trend was seen in elderlyhealthy volunteers in previous studies. No difference was found in otherEGG parameters between the two groups. Conclusion: I) Regular gastricslow waves in the fasting and fed state are substantially lower in patientswith functional dyspepsia. 2) Younger patients with functional dyspepsiahave a significantly higher prevalence of tachygastria/tachyarrhythmia inthe fasting state. The exact mechanism is not known. 3) Bradygastria is thepredominant abnormal slow wave during the fasting or fed state in bothgroups.