Determination of pharmacokinetic parameters of phenytoin in Iranian epileptic patients

ABSTRACT

Adjustment of phenytoin dosage in patients is very difficult due to its nonlinear metabolism and patient to patient variation in its kinetics. It has been recommended that the dosage of phenytoin should be adjusted according to its plasma concentration and requirements of the patients. Therefore, the present study was carried out to identify the various factors which may influence the plasma level of this drug. The phenytoin plasma concentration was determined in 91 patients with steady-state concentrations according to the EMIT method. In a further 14 patients, who had recieved at least two different doses of phenytoin, the Km and Vmax of phenytoin metabolism were determined according to Mullen's direct linear plot. The results of this study showed that the plasma level of phenytoin was below the therapeutic level in 62 [68.2%] of the patients and above the therapeutic level in 8 [8.8%]. Statistical analysis did not show any correlation between plasma level and factors such as sex, age, or type of drug administered. Only a small correlation was found between dosage and plasma level. The Km of phenytoin metabolism in the group studied was found to be in the range of 1.8-26micro g/ml and that of Vmax in the range of 5.33-13.88 mg/kg/day. The mean values of Km [8.4 +/- 1.7 micro g/ml] and Vmax [7.3 +/- 0.58 mg/kg/day] were slightly higher than reported values in the literature [5.7 +/- 2.9 micro g/ml and 5.9 +/- 1.2 mg/kg/day, respectively]. However, this difference was not statistically significant