Phenytoin dosage adjustment in Saudi epileptics: utilization of steady-state pharmacokinetic parameters

We determined the Michaelis-Menten parameters (V-max and K-m) in 271 Saudi epileptic patients having generalized tonic-clonic seizures and who were treated with phenytoin (PHT) using high pressure liquid chromatography (HPLC). The patients comprised 150 (55.4%) males and 121 (44.6%) females, with a mean age of 31.7 years (SD = 18.5). The mean V-max for subjects less than 16 years of age was 10.35 mg/kg/day (SD = 0.73, range = 3.77-17.01), while for those above 16 years, the mean value was 7.99 mg/kg/day (SD = 0.15, range = 3.68-15.95). The difference was statistically significant (P < 0.001). V-max was positively correlated with weight (r = 0.953), but negative with age (r = -0.903). K-m values ranged from 1.01-20.87 mg/litre. The adult K-m mean of 6.52 mg/l (SD = 0.24) was significantly higher than the mean of 4.79 mg/l (SD = 0.40) for pediatric patients (P < 0.01), but K-m was correlated neither with age nor with weight. Our results showed no difference between the predicted and observed serum PHT concentrations in both the pediatric and adult patients when the respective age group K-m and V-max values were used to adjust PHT doses. The pediatric cases, however, required 30% more PHT per kilogram of body weight than the adults for the achievement of similar serum concentrations. Eur J Neurol 6:331-334 (C) 1999 Lippincott Williams & Wilkins.