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

• Published in: Drug metabolism and pharmacokinetics 2011-01, Vol.26 (1), p.71-78
• Main Authors: Ishida, Kazuya, Kaneda, Hisashi, Uemura, Osamu, Ushijima, Katsumi, Ohta, Kazuhide, Goto, Yoshimitsu, Satomura, Kenichi, Shimizu, Masaki, Fujieda, Mikiya, Morooka, Masashi, Yamada, Takuji, Yamada, Masayoshi, Wada, Naohiro, Takaai, Mari, Hashimoto, Yukiya
• Format: Article
• Language: English
• Subjects: Adolescent; Area Under Curve; area under the curve; Bayes Theorem; Bayesian analysis; Child; Child, Preschool; Female; Humans; Immunosuppressive Agents - pharmacokinetics; Kidney Diseases - drug therapy; limited sampling model; Male; maximal drug concentration; mizoribine; Ribonucleosides - pharmacokinetics
• ISSN: 1347-4367; 1880-0920
• DOI: 10.2133/dmpk.DMPK-10-RG-077

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 6hr 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 (3hr) sampling design. On the other hand, the AUC estimation performance seemed to be inadequate in the 1-point (3hr) sampling design; however, it improved markedly in the 2-point (3 and 6hr) sampling design. These findings suggested that the 1-point (3hr) sampling design is promising for approximate C max estimation, but that the 2-point (3 and 6hr) sampling design is preferable to estimate the AUC of mizoribine.