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Mizoribine requires individual dosing due to variation of bioavailability.
MedLine Citation:
PMID:  23039376     Owner:  NLM     Status:  Publisher    
BACKGROUND: Mizoribine (MZR) is an immunosuppressant used for the treatment of glomerular diseases, but there are few reports on the pharmacokinetics of MZR in children. METHODS: First, we performed a pharmacokinetic study on nine childhood-onset glomerular disease patients. The MZR dosages ranged from 1.8-14.5 mg/kg/dose. Pharmacokinetic parameters were analyzed using 38 MZR concentration-time curves. Second, nine patients who were newly treated with MZR were enrolled to validate the findings obtained from prior investigation. RESULTS: In the prior study, peak serum MZR concentration (C(max) ) was dose-dependent in each patient. Although proportionality between dosage and C(max) was observed in each patient, the regression coefficient was in a wide range from 0.075 to 1.04 and was specific to each patient. This variability was likely caused by individual variation of bioavailability. When the optimal time point to monitor C(max) was investigated, the time-to-reach peak serum MZR concentration (T(max) ) was similar among all the patients, which was from 2.5 to 3.5 hours after administration of MZR. T(max) was most frequently observed at 3 hours and the serum MZR concentration ratio relative to C(max) at 3 hours was also highest (0.93 ± 0.07). In the following study, it was validated that monitoring C(3) is reproducible and reliable after adjusting the dosage of MZR to obtain target serum concentration. CONCLUSION: Individual dosing is required to optimize C(max) in childhood-onset glomerular disease patients. The safe dosage of MZR for each patient could be predicted by evaluating the serum MZR concentration 3 hours after administration.
Toshiya Fuke; Yoshifusa Abe; Satoshi Hibino; Takeshi Mikawa; Takako Saito; Shunsuke Sakurai; Shuichiro Watanabe; Jun-Ichiro Murayama; Kazuo Itabashi; Yasuko Nakano
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-8
Journal Detail:
Title:  Pediatrics international : official journal of the Japan Pediatric Society     Volume:  -     ISSN:  1442-200X     ISO Abbreviation:  Pediatr Int     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100886002     Medline TA:  Pediatr Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 The Authors. Pediatrics International © 2012 Japan Pediatric Society.
Department of Hospital Pharmaceutics, School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, Japan; Department of Pharmacogenomics, School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, Japan.
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