Hisashi Kaneda1, Masaki Shimizu2, Kazuhide Ohta3, Katsumi Ushijima4, Yoshimitsu Gotoh5, Kenichi Satomura6, Takuhito Nagai7, Mikiya Fujieda8, Masashi Morooka9, Takuji Yamada5, Masayoshi Yamada10, Naohiro Wada10, Mari Takaai11, Yukiya Hashimoto11, Osamu Uemura7. 1. Department of Pediatrics, Toyama City Hospital, 2-1 Imaizui-Hokubu-machi, Toyama, 939-8511, Japan. 2. 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. 3. Department of Pediatrics, Kanazawa Medical Center, 1-1 Shimoishibiki-cho, Kanazawa, 920-8650, Japan. 4. Department of Pediatrics, Yokkaichi Municipal Hospital, 2-2-37 Shibata, Yokkaichi, 510-8567, Japan. 5. Kidney Center Pediatrics, Nagoya Daini Red Cross Hospital, 2-9 Myoken-cho, Showa-ku, Nagoya, 466-8650, Japan. 6. Department of Pediatric Nephrology and Metabolism, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi, 594-1101, Japan. 7. Department of Pediatric Nephrology, Aichi Children's Health and Medical Center, 1-2 Osakada, Morioka-cho, Obu, 474-8710, Japan. 8. Department of Pediatrics, Kochi Medical School, Kochi University, Oko-cho Kohasu, Nankoku, 783-8505, Japan. 9. Department of Pediatrics, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Japan. 10. Department of Pediatric Nephrology, Shizuoka Children's Hospital, 860 Urushiyama, Aoi-ku, Shizuoka, 420-8660, Japan. 11. Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
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 (C max) 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 C max by age group. No relationship was observed between the administration method of MZR and serum concentration. CONCLUSION: 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.
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 (C max) 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 C max by age group. No relationship was observed between the administration method of MZR and serum concentration. CONCLUSION: 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.
Entities:
Keywords:
Drug monitoring; Mizoribine; Pediatrics; Therapeutics
Authors: K Sonda; K Takahashi; K Tanabe; S Funchinoue; Y Hayasaka; H Kawaguchi; S Teraoka; H Toma; K Ota Journal: Transplant Proc Date: 1996-12 Impact factor: 1.066
Authors: K Yoshioka; Y Ohashi; T Sakai; H Ito; N Yoshikawa; H Nakamura; T Tanizawa; H Wada; S Maki Journal: Kidney Int Date: 2000-07 Impact factor: 10.612