title: Pharmacokinetic variability of routinely administered bisoprolol in middle-aged and elderly Japanese patients.
abstract: The nonlinear mixed effects model (NONMEM) was used to analyze the pharmacokinetics of routinely administered bisoprolol in middle-aged and elderly Japanese patients. The subjects consisted of 29 males and 11 females with a mean age of 63.5+/-10.1. Data on the plasma concentration of bisoprolol from 94 blood samples obtained at steady-state following repetitive oral administration were analyzed using the NONMEM program, where a one-compartment model with repetitive bolus dosing was parameterized in terms of oral clearance (CL/F) and apparent volume of distribution (V/F). Individual CL/F values were correlated with body weight (WT) and creatinine clearance (CLcr). The relation between CLcr and the CL/F of bisoprolol was not altered by the CYP2D6 and CYP2C19 genotypes, gender, or age. The mean CL/F value estimated with NONMEM was 0.0612.WT+1.15.CLcr (l/h), and the mean V/F value was 2.61.WT (l). The residual interindividual variability of CL/F and V/F were 22.0% and 12.6%, respectively. The pharmacokinetic variability of bisoprolol is small even in routinely treated Japanese patients, provided that both body weight and renal function are taken into account for the prediction of oral clearance of the drug.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Taguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Nozawa
authors.forename: Akihiko
authors.initials: A
authors.lastname: Igawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.forename: Chihiro
authors.initials: C
authors.lastname: Takesono
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Tahara
authors.forename: Yukiya
authors.initials: Y
authors.lastname: Hashimoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D044466:Asian People / Q000235:genetics*; D017298:Bisoprolol / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D014644:Genetic Variation / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D017298:Bisoprolol