Evaluation of Limited Sampling Designs to Estimate Maximal Concentration and Area under the Curve of Mizoribine in Pediatric Patients with Renal Disease

Kazuya ISHIDA; Hisashi KANEDA; Osamu UEMURA; Katsumi USHIJIMA; Kazuhide OHTA; Yoshimitsu GOTO; Kenichi SATOMURA; Masaki SHIMIZU; Mikiya FUJIEDA; Masashi MOROOKA; Takuji YAMADA; Masayoshi YAMADA; Naohiro WADA; Mari TAKAAI; Yukiya HASHIMOTO

doi:10.2133/dmpk.DMPK-10-RG-077

Regular Article

Evaluation of Limited Sampling Designs to Estimate Maximal Concentration and Area under the Curve of Mizoribine in Pediatric Patients with Renal Disease

Kazuya ISHIDA, Hisashi KANEDA, Osamu UEMURA, Katsumi USHIJIMA, Kazuhide OHTA, Yoshimitsu GOTO, Kenichi SATOMURA, Masaki SHIMIZU, Mikiya FUJIEDA, Masashi MOROOKA, Takuji YAMADA, Masayoshi YAMADA, Naohiro WADA, Mari TAKAAI, Yukiya HASHIMOTO

Author information

Kazuya ISHIDA
Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama
Hisashi KANEDA
Department of Pediatrics, Toyama City Hospital
Osamu UEMURA
Department of Pediatric Nephrology, Aichi Children's Health and Medical Center
Katsumi USHIJIMA
Department of Pediatrics, Yokkaichi City Hospital
Kazuhide OHTA
Department of Pediatrics, Kanazawa Medical Center
Yoshimitsu GOTO
Kidney Center Pediatrics, Nagoya Daini Red Cross Hospital
Kenichi SATOMURA
Division of Nephrology and Bone Metabolism, Department of Pediatrics, Osaka Medical Center and Research Institute for Maternal and Child Health
Masaki SHIMIZU
Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University
Mikiya FUJIEDA
Department of Pediatrics, Kochi Medical School, Kochi University
Masashi MOROOKA
Department of Pediatrics, Fujita Health University
Takuji YAMADA
Kidney Center Pediatrics, Nagoya Daini Red Cross Hospital
Masayoshi YAMADA
Department of Pediatric Nephrology, Shizuoka Children's Hospital
Naohiro WADA
Department of Pediatric Nephrology, Shizuoka Children's Hospital
Mari TAKAAI
Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama
Yukiya HASHIMOTO
Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama

Keywords: Bayesian analysis, limited sampling model, mizoribine, maximal drug concentration, area under the curve

JOURNAL FREE ACCESS

2011 Volume 26 Issue 1 Pages 71-78

DOI https://doi.org/10.2133/dmpk.DMPK-10-RG-077

View "Advance Publication" version (October 22, 2010).

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Abstract

The aim of this study was to evaluate limited sampling designs to estimate the maximal concentration (C_max) and area under the curve (AUC) of mizoribine in pediatric patients with renal disease. We utilized 48 serum mizoribine concentration profiles obtained from the full (6-point) sampling pharmacokinetic test, and estimated 48 individual C_max and AUC values accurately with Bayesian analysis using the full sampling data. We then developed limited sampling models (LSM) for C_max and AUC using 1–4 serum mizoribine concentration data points. The C_max and AUC estimation performance of the Bayesian and LSM analysis was fairly good in the 3-point (2, 3, and 6 hr after the dose) sampling design. In addition, the C_max estimation performance of the Bayesian and LSM analysis deteriorated only marginally even in the 1-point (3 hr) sampling design. On the other hand, the AUC estimation performance seemed to be inadequate in the 1-point (3 hr) sampling design; however, it improved markedly in the 2-point (3 and 6 hr) sampling design. These findings suggested that the 1-point (3 hr) sampling design is promising for approximate C_max estimation, but that the 2-point (3 and 6 hr) sampling design is preferable to estimate the AUC of mizoribine.

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