The true distribution volume and bioavailability of mizoribine in children with chronic kidney disease

• Published in: Clinical and experimental nephrology Vol. 21; no. 5; pp. 884 - 888
• Main Authors: Nagai, Takuhito, Uemura, Osamu, Kaneda, Hisashi, Ushijima, Katsumi, Ohta, Kazuhide, Gotoh, Yoshimitsu, Satomura, Kenichi, Shimizu, Masaki, Fujieda, Mikiya, Morooka, Masashi, Yamada, Takuji, Yamada, Masayoshi, Wada, Naohiro, Hashimoto, Yukiya
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.10.2017; Springer Nature B.V
• Subjects: Adolescent; Age; Age Factors; Bayes Theorem; Bayesian analysis; Bioavailability; Biological Availability; Child; Child, Preschool; Children; Drug Dosage Calculations; Female; Glomerular Filtration Rate; Humans; Immunosuppressive agents; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - pharmacokinetics; Immunosuppressive Agents - urine; Infant; Kidney - physiopathology; Kidney diseases; Kidney transplantation; Male; Medicine; Medicine & Public Health; Models, Biological; Nephrology; Original Article; Pediatrics; Pharmacodynamics; Pharmacokinetics; Population studies; Renal Agents - administration & dosage; Renal Agents - pharmacokinetics; Renal Agents - urine; Renal Elimination; Renal Insufficiency, Chronic - diagnosis; Renal Insufficiency, Chronic - drug therapy; Renal Insufficiency, Chronic - physiopathology; Renal Insufficiency, Chronic - urine; Ribonucleosides - administration & dosage; Ribonucleosides - pharmacokinetics; Ribonucleosides - urine; Studies; Urine; Urology; Young Adult; Distribution volume; Bioavailability; Pharmacokinetics; Child; Mizoribine
• ISSN: 1342-1751; 1437-7799
• DOI: 10.1007/s10157-016-1353-x

Background Mizoribine (MZR) is used kidney transplant and various kidney diseases. However, few studies reported the association between pharmacokinetics and pharmacodynamics. The Pharmacokinetics Study Group for Pediatric Kidney Disease (PSPKD) used population pharmacokinetics (PPK) analysis and Bayesian analysis to investigate the usefulness of MZR. In this study, the fact that almost all MZR are excreted unchanged in urine was used to calculate its bioavailability ( F ) and true distribution volume ( V d ), and analyzed these correlation with age. Methods Ishida et al. reported a PPK analysis by the PSPKD. In the present study, 71 samples extracted from their study population of 105 pediatric chronic kidney disease patients aged between 1 and 20 years were investigated. The bioavailability was calculated by measuring total excreted MZR in 24 h urine samples, and this was compared to the oral dosage. The apparent distribution volume ( V d / F ) obtained from Bayesian analysis was then used to calculate true distribution volume ( V d ), and the correlation of each parameter with age was investigated. Results The median dose of MZR per weight was 5.17 mg/kg/day. Median bioavailability was 32.02%. Median V d per weight was 0.46 L/kg. There was a significant, weakly positive correlation between bioavailability and age ( p  = 0.026). There was also a significant, weakly negative correlation between V d per weight and age ( p  = 0.003). Conclusion Bioavailability and V d per weight tended to decrease depending on age. The younger patient required larger dose required to obtain the maximum effect from MZR, and this is important for immunosuppressive therapy.