caa a22 4500 445882840 CHVBK 20180317145549.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s10157-011-0487-0 doi (NATIONALLICENCE)springer-10.1007/s10157-011-0487-0 Population pharmacokinetics of mizoribine in adult recipients of renal transplantation [Elektronische Daten] [Kazuya Ishida, Masahiko Okamoto, Michio Ishibashi, Yukiya Hashimoto] 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 (25-450mg/day). The range of creatinine clearance (CLcr) was 7.6−136.1mL/min (mean 49.2mL/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 0.983h−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×WTL. Oral clearance (CL/F) was modeled as a function of creatinine clearance (CLcr), and the mean value was estimated to be 1.80×CLcr×60/1000L/h. In addition, there was a strong correlation between CLcr-corrected CL/F and WT-corrected 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. Japanese Society of Nephrology, 2011 Mizoribine nationallicence Population pharmacokinetics nationallicence Bioavailability nationallicence Renal transplantation nationallicence Ishida Kazuya Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, 930-0194, Toyama, Japan aut Okamoto Masahiko Department of Organ Interaction Research Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajiicho, Kawaramachi-Hirokoji, Kamigyo-ku, 602-8566, Kyoto, Japan aut Ishibashi Michio Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Nara, Japan aut Hashimoto Yukiya Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, 930-0194, Toyama, Japan aut Clinical and Experimental Nephrology Springer Japan 15/6(2011-12-01), 900-906 1342-1751 15:6<900 2011 15 10157 https://doi.org/10.1007/s10157-011-0487-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10157-011-0487-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ishida Kazuya Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, 930-0194, Toyama, Japan aut NATIONALLICENCE 700 1- Okamoto Masahiko Department of Organ Interaction Research Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajiicho, Kawaramachi-Hirokoji, Kamigyo-ku, 602-8566, Kyoto, Japan aut NATIONALLICENCE 700 1- Ishibashi Michio Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Nara, Japan aut NATIONALLICENCE 700 1- Hashimoto Yukiya Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, 930-0194, Toyama, Japan aut NATIONALLICENCE 773 0- Clinical and Experimental Nephrology Springer Japan 15/6(2011-12-01), 900-906 1342-1751 15:6<900 2011 15 10157 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer