Population Pharmacokinetics of Phenytoin in Epileptic Patients

Phenytoin exhibits non-linear pharmacokinetics, narrow therapeutic index, marked inter-individual variations and causes wide variety of adverse effects which warrants the need for monitoring. The present study was taken up to monitor serum concentrations and to carry out preliminary pharmacokinetic modelling. HPLC method was standardized to estimate the serum concentration of phenytoin. Blood samples were withdrawn from the patients after the steady state has been reached. In the study period of 8 months, 20 patients were enrolled out of whom, 10 patients received oral phenytoin whereas 10 were given IV infusion. It was observed that there were a lot of variations in the PHT serum concentrations in different patients with peak values ranging from 5.11 to 80.59 µg/ml and trough concentrations ranging from 1.06 to 92.10 µg/ml. However seizure was well controlled in all the patients with no major toxicities observed. Preliminary population pharmacokinetic modelling was attempted using NONMEM, due to small sample size a robust model could not be developed that gives a definite correlation between the variables and pharmacokinetic parameters.