Three Michaelis-Menten pharmacokinetic dosing methods compared with physician dosing of phenytoin in an outpatient neurology practice

Abstract

We compared predicted phenytoin serum concentrations using three Michaelis-Menten pharmacokinetic dosing methods with actual concentrations obtained from physician dosing in an outpatient neurology practice. Method 1 used population estimates for the Michaelis-Menten constant (Km) and maximum velocity (Vmax), method 2 used one dose and serum concentration pair to determine Vmax, and method 3 used two dose-concentration pairs to determine both Km and Vmax. In addition, physician doses were compared with pharmacokinetically calculated doses. Records of patients who received at least two phenytoin doses followed by two serum concentration determinations were reviewed. Data on age, gender, weight, physician doses, and resultant serum concentrations were collected. Pearson's correlation coefficient was used to compare physician maintenance doses with pharmacokinetically calculated predicted doses, whereas actual and predicted serum concentration data were used to determine precision and bias associated with each of the three methods. Actual serum concentrations fell into therapeutic range more frequently than predicted values in all but one comparison (method 3). Predicted and actual phenytoin doses were significantly correlated only with method 2. Only one of the three Michaelis-Menten pharmacokinetic dosing methods evaluated (method 3) was more predictive than physician phenytoin dosing.