Population pharmacokinetics of mizoribine in pediatric patients with kidney disease |
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| Authors: | Hisashi Kaneda Masaki Shimizu Kazuhide Ohta Katsumi Ushijima Yoshimitsu Gotoh Kenichi Satomura Takuhito Nagai Mikiya Fujieda Masashi Morooka Takuji Yamada Masayoshi Yamada Naohiro Wada Mari Takaai Yukiya Hashimoto Osamu Uemura |
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| Institution: | 1.Department of Pediatrics,Toyama City Hospital,Toyama,Japan;2.Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences,Kanazawa University,Kanazawa,Japan;3.Department of Pediatrics,Kanazawa Medical Center,Kanazawa,Japan;4.Department of Pediatrics,Yokkaichi Municipal Hospital,Yokkaichi,Japan;5.Kidney Center Pediatrics,Nagoya Daini Red Cross Hospital,Nagoya,Japan;6.Department of Pediatric Nephrology and Metabolism,Osaka Medical Center and Research Institute for Maternal and Child Health,Izumi,Japan;7.Department of Pediatric Nephrology,Aichi Children’s Health and Medical Center,Obu,Japan;8.Department of Pediatrics, Kochi Medical School,Kochi University,Nankoku,Japan;9.Department of Pediatrics,Fujita Health University,Toyoake,Japan;10.Department of Pediatric Nephrology,Shizuoka Children’s Hospital,Shizuoka,Japan;11.Graduate School of Medicine and Pharmaceutical Sciences,University of Toyama,Toyama,Japan |
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| Abstract: | BackgroundThe present study aimed to obtain information enabling optimisation of the clinical effect of mizoribine (MZR) in pediatric patients with kidney disease.MethodsA total of 105 pediatric patients with kidney disease treated at our institutions were enrolled. Kidney transplant patients were excluded. Population pharmacokinetic analysis of MZR was performed based on serum concentration data. Area under the curve from time zero to infinity (AUC∞) and maximal concentration (C max) were calculated by Bayesian analysis.ResultsIn children, the appearance of MZR in the blood tended to be slower and the subsequent rise in blood concentration tended to be more sluggish, compared to healthy adults. Apparent volume of distribution and oral clearance were also higher in children compared to adults. A significant positive correlation was observed between patient age and AUC∞. There were significant differences of AUC∞ and C max by age group. No relationship was observed between the administration method of MZR and serum concentration.ConclusionThe pharmacokinetics of MZR was different in children compared to adults. To obtain the expected clinical efficacy, the regular MZR dosage schedule (2–3 mg/kg/day) might be insufficient for pediatric patients. In particular, younger patients might require a higher dosage of MZR per unit body weight. |
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