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

We compared predicted phenytoin serum concentrations using three Michaelis- Menten pharmacokinetic dosing methods with actual concentrations obtained f rom physician dosing in an outpatient neurology practice. Method 1 used pop ulation estimates for the Michaelis-Menten constant (K-m) and maximum veloc ity (V-max), method 2 used one dose and serum concentration pair to determi ne V-max, and method 3 used two dose-concentration pairs to determine both K-m and V-max. In addition, physician doses were compared with pharmacokine tically calculated doses. Records of patients who received at least two phe nytoin doses followed by two serum concentration determinations were review ed. Data on age, gender, weight, physician doses, and resultant serum conce ntrations were collected. Pearson's correlation coefficient was used to com pare physician maintenance doses with pharmacokinetically calculated predic ted 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 tha n predicted values in all but one comparison (method 3). Predicted and actu al phenytoin doses were significantly correlated only with method 2. Only o ne of the three Michaelis-Menten pharmacokinetic dosing methods evaluated ( method 3) was more predicyive than physician phenytoin dosing.