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Mizoribine requires individual dosing due to variation of bioavailability
Author(s) -
Fuke Toshiya,
Abe Yoshifusa,
Hibino Satoshi,
Takeshi Mikawa,
Saito Takako,
Sakurai Shunsuke,
Watanabe Shuichiro,
Murayama JunIchiro,
Itabashi Kazuo,
Nakano Yasuko
Publication year - 2012
Publication title -
pediatrics international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.49
H-Index - 63
eISSN - 1442-200X
pISSN - 1328-8067
DOI - 10.1111/j.1442-200x.2012.03733.x
Subject(s) - medicine , mizoribine , dosing , pharmacokinetics , bioavailability , dose , clearance , serum concentration , renal function , pharmacology , urology
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 to 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 h after administration of MZR . T max was most frequently observed at 3 h and the serum MZR concentration ratio relative to C max at 3 h 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 h after administration.