title: Population pharmacokinetics of mizoribine in pediatric patients with kidney disease.
abstract: BACKGROUND
  The present study aimed to obtain information enabling optimisation of the clinical effect of mizoribine (MZR) in pediatric patients with kidney disease.
  
  
  METHODS
  A 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 (Cmax) were calculated by Bayesian analysis.
  
  
  RESULTS
  In 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 Cmaxby age group. No relationship was observed between the administration method of MZR and serum concentration.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Pediatrics, Toyama City Hospital, 2-1 Imaizui-Hokubu-machi, Toyama, 939-8511, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Kaneda
authors.affiliation: Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8640, Japan. shimizum@staff.kanazawa-u.ac.jp.
authors.forename: Masaki
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Department of Pediatrics, Kanazawa Medical Center, 1-1 Shimoishibiki-cho, Kanazawa, 920-8650, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Ohta
authors.affiliation: Department of Pediatrics, Yokkaichi Municipal Hospital, 2-2-37 Shibata, Yokkaichi, 510-8567, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Ushijima
authors.affiliation: Kidney Center Pediatrics, Nagoya Daini Red Cross Hospital, 2-9 Myoken-cho, Showa-ku, Nagoya, 466-8650, Japan.
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Gotoh
authors.affiliation: Department of Pediatric Nephrology and Metabolism, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi, 594-1101, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Satomura
authors.affiliation: Department of Pediatric Nephrology, Aichi Children's Health and Medical Center, 1-2 Osakada, Morioka-cho, Obu, 474-8710, Japan.
authors.forename: Takuhito
authors.initials: T
authors.lastname: Nagai
authors.affiliation: Department of Pediatrics, Kochi Medical School, Kochi University, Oko-cho Kohasu, Nankoku, 783-8505, Japan.
authors.forename: Mikiya
authors.initials: M
authors.lastname: Fujieda
authors.affiliation: Department of Pediatrics, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Morooka
authors.affiliation: Kidney Center Pediatrics, Nagoya Daini Red Cross Hospital, 2-9 Myoken-cho, Showa-ku, Nagoya, 466-8650, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Pediatric Nephrology, Shizuoka Children's Hospital, 860 Urushiyama, Aoi-ku, Shizuoka, 420-8660, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Department of Pediatric Nephrology, Shizuoka Children's Hospital, 860 Urushiyama, Aoi-ku, Shizuoka, 420-8660, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Wada
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Takaai
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Yukiya
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Department of Pediatric Nephrology, Aichi Children's Health and Medical Center, 1-2 Osakada, Morioka-cho, Obu, 474-8710, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Uemura
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000367:Age Factors; D019540:Area Under Curve; D001499:Bayes Theorem; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D054796:Drug Dosage Calculations; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007223:Infant; D007408:Intestinal Absorption; D007564:Japan; D007674:Kidney Diseases / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D016014:Linear Models; D008297:Male; D008954:Models, Biological; D012263:Ribonucleosides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D007166:Immunosuppressive Agents; D012263:Ribonucleosides; C010052:mizoribine
keywords: Drug monitoring; Mizoribine; Pediatrics; Therapeutics