Construction of Windows for Pharmacokinetic Sampling

This paper describes a method for the construction of pharmacokinetic sampling windows so that they are around the $D$-optimum time points. Here we consider the situation where a pharmacokinetic (PK) study is accompanied by a dose-finding study in phase I clinical trial. The D-optimal criterion is often used to determine the optimal time for collecting blood samples so that they provide maximum information regarding the population PK parameters. However, collecting blood samples at the D-optimal time points is often difficult. Instead, the sampling time point chosen from a suitable time interval or window can ease the process. The proposed method is conceptually simple and considers the average value and standard deviation of D-optimal time points up to create sampling windows. Random time points can be chosen from these windows then to collect blood samples from the next cohort. The nonlinear random-effects model has been used to model the PK data. Also, we employ the continual reassessment method for dose allocation to the patients. Comparisons of the accuracy and precision for the PK parameter estimates obtained at the D-optimal and random time points are also presented. The results are convincing enough to suggest the proposed method as a useful tool for blood sample collection.