Phenytoin Dosage Adjustment Method Using Population Clearance

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Phenytoin (PHT) is a commonly used drug in children and abults, but it is often difficult to adjust the dosage to attain therapeutic drug concentrations due to the nonlinear nature of PHT metabolism. Therefore, many techniques have been proposed to aid dosage adjustment based on single-point PHT concentration determined at the steady state. We have derived a simple equation to predict PHT dosage in a patient in whom one steady-state serum concentration is known. This equation is based on a power relationship between PHT clearance (CL; l/d) and PHT concentration determined at the steady state (C_<ss>; μg/ml).CL=D/C_<ss>=a・C_<ss>^b (1)D_n=D_o・C_o^<-(b+1)>・C_d^<(b+1)> (2) where D is the PHT dose (mg/d), D_o is the original dose, D_n is the new dose, C_o is the original C_<ss>, and C_d is the desired C_<ss>.We retrospectively investigated the values of a and b in a population of 40 outpatients who had three or more reliable measurements of C_<ss> in serum, measured while they were taking different daily doses. The a and b values were estimated to be 114.34 and -0.6786,respectively (n=126; r=0.871). Graves et al. have previously derived a similar equation based on an exponential relation between CL of PHT and C_<ss> in 59 patients (a=133.03,b=-0.804). The predictive ability of this equation was compared with the results of Graves's method and the Bayesian feedback method using retrospective data from 70 patients. This equation allowed the prediction of a dose needed to produce a desired steady-state concentration with satisfactory error, being as effective as the Bayesian feedback method for therapeutic drug monitoring.
公益社団法人日本薬学会の論文
1990-02-25

Phenytoin Dosage Adjustment Method Using Population Clearance

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