Phenytoin Michaelis-Menten pharmacokinetics in Saudi patients

The Michaelis-Menten pharmacokinetic parameters Vmax and Km were calculated for 17 epileptic Saudi patients receiving phenytoin. Their ages ranged from 2.5 to 47 years (mean 21 years) and their weight ranged from 9.5 to 80 kg (mean 53 kg). Eight were females and 9 were males. Phenytoin serum concentrations at steady-state were measured using the fluorescence polarization immunoassay. The mean (+/- s.e.m) for Vmax and Km were, respectively, 10.93 +/- 0.78 mg.kg-1.day-1 and 7.75 +/- 0.66 mg.l-1 for children and 6.91 +/- 0.4 mg.kg-1.day-1 and 6.44 +/- 1.01 mg.l-1 for adults. The derived values of Vmax and Km were used to predict the steady-state serum phenytoin concentrations following a change in dose for 7 adult patients. There was a highly significant correlation between observed and predicted steady-state concentrations (r = 0.968, p less than 0.001). Linear regression analysis of Vmax vs age revealed a significant decline in Vmax with age (r = 0.877, p less than 0.01). There is a significant increase in Vmax with weight (r = 0.816, p less than 0.01). A plot of Km vs age and weight showed a poor correlation (r = 0.302, r = 0.218, respectively) and a large amount of variability. Based on this data, the daily phenytoin doses for children and adults are 7.21 mg.kg-1 and 4.83 mg.kg-1, respectively, in order to achieve and maintain a steady-state phenytoin concentration of 15 mg.l-1.