Evaluation of limited sampling designs to estimate maximal concentration and area under the curve of mizoribine in pediatric patients with renal disease

Summary: The aim of this study was to evaluate limited sampling designs to estimate the maximal concen- tration (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 pharmaco- kinetic 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 14 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.