Phenytoin clearances in a compliant population: description and application.

The saturable elimination kinetics of phenytoin (PHT) makes accurate dosing difficult. A simple equation has been derived to predict dosing requirements if one dose--steady-state serum concentration pair is known [new dose = first dose X Cpss (desired)0.2 X Cpss (achieved)-0.2]. This equation is based on an exponential relation between 177 pairs of PHT clearance and steady-state serum concentrations from 59 compliant patients. To evaluate this population clearance method (PCM), patients were drawn from two independent populations (Minnesota and Iowa, U.S.A.). Predicted doses obtained from PCM were compared with predictions from Bayesian, average Vmax, and average Km methods. The Bayesian method was the most precise and least biased of all methods, under- and overpredicting doses in equal frequency. PCM was biased to produce underpredictions. However, clinically achievable doses can be obtained by consistently rounding the calculated dose upward. The mean underprediction for the Bayesian method was 6 mg, for PCM 46 mg, for average Vmax 21 mg, and for average Km 11 mg. PCM is relatively precise, somewhat biased, and very easy to use.