The pharmacokinetics of phenytoin in rabbits with hyperlipidemia induced by high-fat diet.

The study was aimed at the evaluation of changes in phenytoin pharmacokinetics during dietary induced hyperlipidemia in rabbits. It was carried out in 17 New Zealand, male rabbits, 3-month old, randomly assigned to two groups: control maintained on standard diet and experimental one fed on a high-fat diet for 2 months. Pharmacokinetic assays were performed in all animals after 2 months of the experiment. Phenytoin was given intragastrically as a single dose 10 mg/kg. Blood for assays was sampled within 48 hours after phenytoin administration. The two compartment open model for extravascular administration was used for calculations. It was demonstrated that the administration of phenytoin in the group of animals with experimental hyperlipidemia was followed by a decrease of the drug concentration in the blood serum, a drop in area under the plasma concentration-time curve, a shorter elimination half-time as well as an increase in total body clearance. All revealed changes suggest that the dietary induced hyperlipidemic state alters the pharmacokinetics of phenytoin, leading to a faster drug elimination from the body.