Population pharmacokinetics of mizoribine in adult recipients of renal transplantation
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Kazuya Ishida Masahiko Okamoto Michio Ishibashi Yukiya Hashimoto
- چاپ و سال / کشور: 2011
Description
Background The aim of the present study was to estimate the population pharmacokinetic parameters of mizoribine in adult recipients of renal transplantation using a nonlinear mixed effects model (NONMEM) program. Methods Pharmacokinetic data for population analysis were retrospectively collected from 114 recipients (66 males and 48 females) routinely treated with oral administration of mizoribine (25–450 mg/day). The range of creatinine clearance (CLcr) was 7.6-136.1 mL/min (mean 49.2 mL/min). Results The pharmacokinetics of mizoribine in adult recipients of renal transplantation was well described by a 1-compartment model with first-order absorption. The mean value of the absorption lag time (ALAG) and absorption rate constant (KA) was estimated to be 0.581 and 0.983 h-1, respectively. Apparent volume of distribution (V/F) was modeled as a function of body weight (WT), and the mean value was estimated to be 0.858 9 WT L. Oral clearance (CL/F) was modeled as a function of creatinine clearance (CLcr), and the mean value was estimated to be 1.80 9 CLcr 9 60/1000 L/h. In addition, there was a strong correlation between CLcr-corrected CL/F and WTcorrected V/F in the adult recipients, indicating large interindividual variability in bioavailability (F) of mizoribine. Conclusion The present findings suggested that not only the rate of renal excretion but also the extent of intestinal absorption of mizoribine is responsible for the large interindividual pharmacokinetic variability of the drug.
Clin Exp Nephrol Received: 11 April 2011 / Accepted: 30 June 2011 Japanese Society of Nephrology 2011
