Phenytoin dosage adjustment method using population clearance.
Phenytoin (PHT) is a commonly used drug in children and adults, 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; 1/d) and PHT concentration determined at the steady state (Css; micrograms/ml). CL = D/Css = a.Css(b) (1) Dn = Do.Co-(b+1).Cd(b+1) (2) where D is the PHT dose (mg/d), Do is the original dose, Dn is the new dose, Co is the original Css, and Cd is the desired Css. We retrospectively investigated the values of a and b in a population of 40 outpatients who had three or more reliable measurements of Css 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 Css 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Yukawa
E
E
Department of Hospital Pharmacy, Kyushu University Hospital, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Higuchi
S
S
Aoyama
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008433:Mathematics; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010672:Phenytoin / Q000008:administration & dosage* / Q000493:pharmacokinetics
D010672:Phenytoin