Comparative analysis of the pharmacokinetic techniques available for individualizing phenytoin dosage

Over the past few years, numerous pharmacokinetic techniques based on Michaelis-Menten principles have been proposed to individualize PHT dosage and predict plasma levels. The choice of one of these techniques for clinical use depends on the number of steady state concentration-versus-dose (Css-D) data pairs that are known in the patient for whom the predictive technique is to be applied. The most frequent clinical situations in which these predictions are made can be divided into three groups for each patient considered--Case A: only one previous Css-D data pair is known; Case B: two previous Css-D data pairs are known; Case C: three previous Css-D data pairs are known. Of the available techniques that can be applied in case A, we compared the population clearance (PC) method and the Bayesian feedback (BF) method. The procedure for comparing the predictive capabilities of these methods was very similar to that adopted in a recent report by Vozeh et al. Our findings showed that the PC method should be preferred for clinical use under this circumstance. Two predictive techniques suitable for use in Case B (BF and Mullen & Foster methods) were compared. In this case, the BF method was shown to be more accurate. As regards Case C, three pharmacokinetic techniques were compared: the Mullen and Foster method, the iterative least-squares (ILS) technique, and the BF method. The ILS technique was found to be the most accurate in this case. Finally, we describe a programmable calculator procedure which uses the PC, BF or ILS methods in Cases A, B and C respectively.(ABSTRACT TRUNCATED AT 250 WORDS)