Takuhito Nagai1, Osamu Uemura2, Hisashi Kaneda3, Katsumi Ushijima4, Kazuhide Ohta5, Yoshimitsu Gotoh6, Kenichi Satomura7, Masaki Shimizu8, Mikiya Fujieda9, Masashi Morooka10, Takuji Yamada11, Masayoshi Yamada12, Naohiro Wada12, Yukiya Hashimoto13. 1. Division of Pediatric Nephrology, Department of Kidney Center, Aichi Medical University, 1-1, Nagakute City, Aichi, 480-1195, Japan. nagataku@aichi-med-u.ac.jp. 2. Department of Pediatric Nephrology, Aichi Children's Health and Medical Center, Obu, Aichi, Japan. 3. Department of Pediatrics, Toyama City Hospital, Toyama, Japan. 4. Department of Pediatrics, Yokkaichi City Hospital, Mie, Japan. 5. Department of Pediatrics, Kanazawa Medical Center, Kanazawa, Japan. 6. Kidney Center Pediatrics, Nagoya Daini Red Cross Hospital, Nagoya, Aichi, Japan. 7. Department of Pediatric Nephrology and Metabolism, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan. 8. Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan. 9. Department of Pediatrics, Kochi Medical School, Kochi University, Kochi, Japan. 10. Department of Pediatrics, Fujita Health University, Toyoake, Aichi, Japan. 11. Department of Pediatrics, Nagoya City West Medical Center, Aichi, Japan. 12. Department of Pediatric Nephrology, Shizuoka Children's Hospital, Shizuoka, Japan. 13. Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Abstract
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.
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 diseasepatients 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.
Entities:
Keywords:
Bioavailability; Child; Distribution volume; Mizoribine; Pharmacokinetics
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