Influence of high fat diet (butter) on pharmacokinetics of phenytoin and carbamazepine

Abstract

The study was carried out to evaluate the effect of butter on the pharmacokinetics of phenytoin and carbamazepine. In a crossover study, phenytoin 30 mg/kg and carbamazepine 56 mg/kg were given orally to New Zealand white rabbits (n = 8 for each drug). Blood samples were drawn at different time intervals from 0-24 h from the marginal ear vein after drug administration. After a washout period of 7 days, butter (5 mg/kg) was administered for 7 days to the animals. On the 8th day, butter and phenytoin or carbamazepine were administered simultaneously and the blood samples were withdrawn at the same time points. Plasma was separated and stored at -20 degrees C until assayed for phenytoin and carbamazepine by HPLC and different pharmacokinetic parameters were calculated. Butter increased the absorption of both phenytoin and carbamazepine, as there was a significant increase in the Cmax and AUC(0-alpha) of both drugs after butter administration. No significant difference in Tmax was observed. In this study, it was found that a high fat diet increases the bioavailability of phenytoin and carbamazepine in New Zealand white rabbits.