Lack of interaction between HEPP, a new antiepileptic agent, and carbamazepine in rabbits.
The effect of the combination of a new anticonvulsant drug HEPP and carbamazepine (CBZ) on the pharmacokinetics of HEPP and CBZ was investigated using rabbits as an animal model. The study was performed in 18 male New Zealand white rabbits which were randomly divided into three groups, according to a balanced incomplete block design of three treatments and two periods. Plasma concentrations for HEPP and CBZ were assayed using HPLC methods. The results showed that the pharmacokinetic parameters C(max), AUC and t(1/2) were not statistically different when HEPP was administered alone and with CBZ, (AUC(0-alpha) 82.86+/-19.40 vs 83.24+/-12.56 microg h ml(-1); t( 1 2 beta) 3.40+/-0.29 vs 3.36+/-0.45 h; C(max) 18.93+/-2.99 vs 19.79+/-2.68 microg ml(-1) and T(max) 1.27+/-0.16 vs 1.22+/-0.11 h for HEPP alone and HEPP plus CBZ respectively. Evaluation of the pharmacokinetic parameters of CBZ showed, AUC(0-inf) 61.5+/-21.7 vs 67.4+/-23.8 microg h ml(-1); t(12) 4.60+/-1.54 vs 4.41+/-1.35 h; C(max) 8.45+/-3.83 vs 8.70+/-2.59 microg ml(-1) when the drug was administered alone and CBZ plus HEPP, respectively. Our data indicate that there is no effect on the pharmacokinetics of either HEPP or CBZ, when they are administered simultaneously.
García
A Luis
AL
Laboratorio de Farmacocinética, Departamento de Farmacología, Facultad de Medicina, UNAM, 04360 México D.F., México.
Medina
R Liz
RL
Pérez
M Rodolfo
MR
Jung
C Helgi
CH
D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D002220:Carbamazepine / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D006207:Half-Life; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D010666:Phenylpropionates / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D011817:Rabbits; D013997:Time Factors
D000927:Anticonvulsants; D007527:Isoenzymes; D010666:Phenylpropionates; D002220:Carbamazepine; C067697:beta-hydroxy-beta-ethyl-phenylpropionamide; D003577:Cytochrome P-450 Enzyme System