Individualization of phenytoin dosage regimens

Abstract

Two methods for arriving at optimum, individual phenytoin dosage regimens have been evaluated in 12 patients. (1) Individual Michaelis-Menten pharmacokinetic parameters for phenytoin were estimated from two reliable steady-state phenytoin serum concentrations resulting from different daily doses: The observed steady-state phenytoin serum levels obtained after 3 to 8 wk of compliance with dosage regimens calculated from the individual pharmacokinetic parameters agreed well with predicted levels (r = 0.824, p < 0.02). The average deviation between observed and predicted levels was 0.04 µg/ml (range, ±3.2 µg/ml). (2) A previously published nomogram for making adjustments in phenytoin dosage regimens: The serum phenytoin concentration actually expected from the dose indicated by the nomogram was calculated using individual pharmacokinetic parameters. The daily dose for one patient would have exceeded his estimated maximal rate of metabolism. The correlation between calculated and predicted phenytoin serum levels in the other 11 patients was weak but significant (r = 0.360, p < 0.05). The average deviation was −3 µg/ml (range, 3.9 to −11.3 µg/ml). It was concluded that the use of individual pharmacokinetic parameters is practical and is also superior to the nomogram.