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Effects of Eslicarbazepine acetate on lipid metabolism profile and sodium values: preliminary outcomes of a prospective study in our patients M. Brienza 1 , C. Davassi 1 , E. Vicenzini 2 , P. Pulitano 2 and O. Mecarelli 2 1 Department of Medico-Surgical Sciences and Biotechnologies - Sapienza University of Rome 2 Department of Neurology and Psychiatry - Sapienza University of Rome Objective To characterize the association among eslicarbazepine acetate (ESL), plasma lipid levels and sodium values and to compare it with previous effects of traditional dibenzazepine drugs. Main references M.V. Vyas, B.A. Davidson, L. Escalaya, J. Costella, G. Saposnik, J. G. Burneo (2015) Antiepileptic drug use for treatment of epilepsy and dyslipidemia: systematic review. Epilepsy Research 113, 44-67. M. Ley, A. Principe, J. Jimenez-Conde, R. Rocamora (2015) Assessing long-term effects of eslicarbazepine acetate on lipid metabolism profile, sodium values and liver function tests. Epilepsy Research 115, 147-152. Results After 6 months of treatment with ESL, we compared the mean total cholesterol and LDL values before and during ESL therapy (total cholesterol values 191.3 ± 29.6 vs 179.7 ± 29.2 mg/dl, p<.0001; LDL 114.58 ± 22.7 vs 103.11 ± 19.46 mg/dl , p<.0001). Furthermore, we evaluated HDL values before and during ESL (57.5± 9.1 vs 63.9 ± 8.3 mg/dl; p.0001). No statistically significant changes were detected in TGC values. ESL was interrupted in 2 patients, after 6 months, because of serious hyponatremia (sodium values < 126 mEq/l) whereas in the other patients, we didn’t observe significant changes of sodium values. Materials and methods This report describes a prospective cohort study currently in progress. We considered 36 adult patients suffered from focal onset epilepsy with and without secondary generalization, in add-on treatment with ESL (800-1200 mg/die). In 8/36 patients, ESL was begun by switching from carbamazepine (CBZ) or oxcarbazepine (OXC). The average time of treatment was 10.5 months (range 6-18). 7 patients (19.4%) were already affected by dyslipidemia, nobody by hyponatremia. The lab values assessed prior and after 6 and 12 months of treatment were natremia, total cholesterol, low and high density lipoproteins (LDL and HDL), triglycerides (TGC). Discussion and Conclusions Severe hyponatremia occurred in 6% of patients and no significant changes of sodium values were found in the other patients. The mean total cholesterol and LDL values of the entire group of patients decreased significantly and HDL increased during treatment with ESL: this suggests that ESL is possibly a safe drug that doesn’t affect negatively the lipid metabolism profile in our patients. This represents a difference from CBZ and OXC maybe because ESL binds plasmatic proteins with lower affinity and it is a weaker inducer of liver metabolism especially for CYP3A4. Recombinant CYP3A4 was shown to convert cholesterol to 4- hydroxycholesterol, whereas no conversion was observed with CYP1A2, CYP2C9, or CYP2B6. However, a greater number of cases and a more prolonged period of observation are necessary to confirm the results and a further step should be to assess biochemical mechanism by which antiepileptic drugs affect the lipid metabolism. Anyhow, a better understanding of the prevalence of dyslipidemia, related to the use of antiepileptic drugs in patients with epilepsy, would facilitate the appropriate management to reduce the risk of vascular diseases in adults, especially if we consider the higher incidence of cardiovascular and cerebrovascular disease in epileptic patients compared with general population. XLVII CONGRESSO NAZIONALE 22-25 OTTOBRE 2016 VENEZIA pt sex age Cholest pre (mg/dl) Cholest post (mg/dl) LDL pre (mg/dl ) LDL post (mg/dl) HDL pre (mg/dl) HDL post (mg/dl) 1 M 45 180 175 130 125 55 55 2 M 53 175 170 120 120 60 65 3 F 38 258 210 169 130 45 65 4 M 25 182 180 130 120 55 60 5 F 40 190 180 125 125 53 60 6 M 32 175 165 98 85 50 55 7 M 40 200 200 130 125 65 70 8 F 70 210 195 96 90 45 55 9 M 23 165 160 67 65 55 58 10 M 46 200 195 130 110 55 70 11 F 20 180 178 125 96 55 65 12 F 50 240 200 160 130 45 55 13 M 41 180 175 120 110 55 60 14 M 38 165 163 110 100 55 55 15 F 78 248 200 161 130 50 55 16 M 31 155 155 98 98 55 60 17 M 65 200 190 160 130 47 55 18 M 71 190 186 110 110 57 57 19 M 30 160 160 120 110 55 55 20 F 20 175 172 110 110 65 75 21 F 37 175 170 110 100 65 65 22 F 62 190 185 100 99 65 70 23 M 45 198 180 130 120 45 55 24 F 20 150 145 95 90 65 70 25 M 22 177 165 99 95 55 62 26 M 53 180 180 97 93 58 60 27 F 47 150 150 95 88 60 65 28 M 29 140 135 87 76 65 70 29 F 69 245 200 125 100 45 60 30 M 63 240 220 120 105 55 65 31 M 39 222 200 153 150 53 63 32 F 23 171 160 71 70 87 90 33 F 43 189 180 90 85 75 81 34 F 40 200 190 95 90 65 75 35 M 35 210 200 110 95 70 75 36 M 40 220 200 120 100 65 72 0 50 100 150 200 250 1 2 3 4 5 6 *p<0.0001 *p<0.0001 *p<0.0001 Pre HDL Total Cholesterol LDL Pre Pre Post Post Post Follow up ≥ 1 y Follow up ≥ 6m

Effects of Eslicarbazepine acetate on lipid metabolism ...congress.wooky.it/web/eventi/NEURO2016/poster/pdf/pst103.pdf · Effects of Eslicarbazepine acetate on lipid metabolism profile

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Page 1: Effects of Eslicarbazepine acetate on lipid metabolism ...congress.wooky.it/web/eventi/NEURO2016/poster/pdf/pst103.pdf · Effects of Eslicarbazepine acetate on lipid metabolism profile

Effects of Eslicarbazepine acetate on lipid metabolism

profile and sodium values: preliminary outcomes of a

prospective study in our patients

M. Brienza 1, C. Davassi 1, E. Vicenzini 2, P. Pulitano 2 and O. Mecarelli 2

1 Department of Medico-Surgical Sciences and Biotechnologies - Sapienza University of Rome2 Department of Neurology and Psychiatry - Sapienza University of Rome

Objective To characterize the association among eslicarbazepine acetate (ESL), plasma lipid levels and sodiumvalues and to compare it with previous effects of traditional dibenzazepine drugs.

Main references

M.V. Vyas, B.A. Davidson, L. Escalaya, J. Costella, G. Saposnik, J. G. Burneo (2015) Antiepileptic drug use for treatment of epilepsy anddyslipidemia: systematic review. Epilepsy Research 113, 44-67.

M. Ley, A. Principe, J. Jimenez-Conde, R. Rocamora (2015) Assessing long-term effects of eslicarbazepine acetate on lipid metabolism profile,sodium values and liver function tests. Epilepsy Research 115, 147-152.

Results After 6 months of treatment with ESL, we comparedthe mean total cholesterol and LDL values before and duringESL therapy (total cholesterol values 191.3 ± 29.6 vs 179.7 ±29.2 mg/dl, p<.0001; LDL 114.58 ± 22.7 vs 103.11 ± 19.46

mg/dl , p<.0001). Furthermore, we evaluated HDL valuesbefore and during ESL (57.5± 9.1 vs 63.9 ± 8.3 mg/dl;

p.0001). No statistically significant changes were detected inTGC values. ESL was interrupted in 2 patients, after 6months, because of serious hyponatremia (sodium values <126 mEq/l) whereas in the other patients, we didn’t observesignificant changes of sodium values.

Materials and methods This report describes a prospective cohort study currently in progress. We considered36 adult patients suffered from focal onset epilepsy with and without secondary generalization, in add-ontreatment with ESL (800-1200 mg/die). In 8/36 patients, ESL was begun by switching from carbamazepine(CBZ) or oxcarbazepine (OXC). The average time of treatment was 10.5 months (range 6-18). 7 patients(19.4%) were already affected by dyslipidemia, nobody by hyponatremia. The lab values assessed prior andafter 6 and 12 months of treatment were natremia, total cholesterol, low and high density lipoproteins (LDL andHDL), triglycerides (TGC).

Discussion and Conclusions

Severe hyponatremia occurred in 6% of patients and nosignificant changes of sodium values were found in the otherpatients. The mean total cholesterol and LDL values of theentire group of patients decreased significantly and HDLincreased during treatment with ESL: this suggests that ESLis possibly a safe drug that doesn’t affect negatively the lipidmetabolism profile in our patients. This represents adifference from CBZ and OXC maybe because ESL bindsplasmatic proteins with lower affinity and it is a weakerinducer of liver metabolism especially for CYP3A4.

Recombinant CYP3A4 was shown to convert cholesterol to 4-hydroxycholesterol, whereas no conversion was observedwith CYP1A2, CYP2C9, or CYP2B6. However, a greaternumber of cases and a more prolonged period of observationare necessary to confirm the results and a further step shouldbe to assess biochemical mechanism by which antiepilepticdrugs affect the lipid metabolism. Anyhow, a betterunderstanding of the prevalence of dyslipidemia, related tothe use of antiepileptic drugs in patients with epilepsy, wouldfacilitate the appropriate management to reduce the risk ofvascular diseases in adults, especially if we consider thehigher incidence of cardiovascular and cerebrovasculardisease in epileptic patients compared with generalpopulation.

XLVII CONGRESSO NAZIONALE22-25 OTTOBRE 2016 – VENEZIA

pt sex ageCholest pre

(mg/dl)

Cholest post

(mg/dl)

LDL pre

(mg/dl)

LDL post (mg/dl)

HDL pre (mg/dl)

HDL post (mg/dl)

1 M 45 180 175 130 125 55 552 M 53 175 170 120 120 60 653 F 38 258 210 169 130 45 654 M 25 182 180 130 120 55 605 F 40 190 180 125 125 53 606 M 32 175 165 98 85 50 557 M 40 200 200 130 125 65 708 F 70 210 195 96 90 45 559 M 23 165 160 67 65 55 5810 M 46 200 195 130 110 55 7011 F 20 180 178 125 96 55 6512 F 50 240 200 160 130 45 5513 M 41 180 175 120 110 55 6014 M 38 165 163 110 100 55 5515 F 78 248 200 161 130 50 5516 M 31 155 155 98 98 55 6017 M 65 200 190 160 130 47 5518 M 71 190 186 110 110 57 5719 M 30 160 160 120 110 55 5520 F 20 175 172 110 110 65 7521 F 37 175 170 110 100 65 6522 F 62 190 185 100 99 65 7023 M 45 198 180 130 120 45 5524 F 20 150 145 95 90 65 7025 M 22 177 165 99 95 55 6226 M 53 180 180 97 93 58 6027 F 47 150 150 95 88 60 6528 M 29 140 135 87 76 65 7029 F 69 245 200 125 100 45 6030 M 63 240 220 120 105 55 6531 M 39 222 200 153 150 53 6332 F 23 171 160 71 70 87 9033 F 43 189 180 90 85 75 8134 F 40 200 190 95 90 65 7535 M 35 210 200 110 95 70 7536 M 40 220 200 120 100 65 72

0

50

100

150

200

250

1 2 3 4 5 6

*p<0.0001

*p<0.0001

*p<0.0001

Pre

HDLTotal Cholesterol LDL

Pre Pre PostPostPost

Fo

llow

up

≥ 1

yF

ollo

w u

p ≥

6m