title: Population pharmacokinetics of higher-dose mizoribine in healthy male volunteers.
abstract: The population pharmacokinetic parameters of mizoribine in healthy subjects were estimated using a nonlinear mixed effects model (NONMEM) program. Pharmacokinetic data for population analysis were obtained in the previous study, in which 24 healthy Caucasian male subjects participated in a single-dose (3, 6, 9, 12 mg/kg) study, and 12 subjects participated in a multiple-dose (6, 12 mg/kg/d) study. The mean value of the absorption lag time, absorption rate constant (KA), and apparent distribution volume (V/F) was estimated to be 0.349 h, 0.869 h-1, and 0.834 l/kg, respectively. Oral clearance (CL/F) was modeled with creatinine clearance (CLcr), and the mean value was estimated to be 1.93.CLcr l/h. In addition, pharmacokinetic parameters in individual 36 subjects were obtained from population estimates according to Bayes' theorem. Pharmacokinetic parameters (KA, V/F, and CL/F) in the single-dose study were almost constant at a dose range of 3-12 mg/kg, and were similar to those in the multiple-dose study. These findings indicated that the pharmacokinetics of mizoribine is well described by a simple one-compartment model with first-order absorption.
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Toyama, Japan.
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Honda
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Itoh
authors.forename: Tadakiyo
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yukiya
authors.initials: Y
authors.lastname: Hashimoto
mesh_terms: D000328:Adult; D001499:Bayes Theorem; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012263:Ribonucleosides / Q000493:pharmacokinetics*
chemical_list: D007166:Immunosuppressive Agents; D012263:Ribonucleosides; C010052:mizoribine