The Current State and Future Prospects of Population Pharmacokinetic Research in Post-marketing Clinical Studies in Japan

Abstract

Population pharmacokinetics (PPK) is a useful approach to the evaluation of drug pharmacokinetics in patients and is a widely used method for the evaluation of pharmacokinetics in clinical trials. PPK uses a statistical model to calculate population parameters, their variance, and covariates from sparse and unbalanced data in a large target population. Population parameters can subsequently be used to establish individual prescribing regimens for specific patients. Post-marketing clinical studies using PPK analysis have been reported by medical and academic institutions in order to complement the poor pharmacokinetics information, thus increasing the available pharmacokinetics information. However, because, in many cases, PPK information is not indicated in the package insert (PI), pharmacokinetics information such as pharmacokinetics parameters and associated variable factors is insufficient. We investigated what kind of new information was obtained in the post-marketing clinical studies using PPK analysis and whether these PPK results were described in Japan PI and/or interview form (IF). We showed that many post-marketing clinical studies were conducted as a single-center and observational study in order to supplement deficient pharmacokinetics data. Also, most PPK results obtained from post-marketing studies were not included in Japan PI and/or IF presumably due to lack of quality of PPK models. If sufficient post-marketing clinical studies using high-quality PPK models are performed, PPK models based on patients with diverse backgrounds, which take inter-individual variability into consideration, can be constructed and PPK information can contribute to the proper use of drugs and the promotion of individualized treatment strategies.