SY18-1Summary of Careful Administration Cases: PK/PD, Genetic polymorphism

Abstract Pharmacokinetics (PK) is affected by aging, organ functions, concomitant drugs, etc.; hence, determining the dose and target blood concentration from PK/PD analysis based on pharmacodynamics (PD) that uses effectiveness/safety as an indicator is essential to the implementation of personalized medicine. In the Phase I trials of clinical pharmacology studies, the subjects have normal organ functions and were relatively young patients; hence, there are very few reports of careful administration cases, such as with elderly people and patients with organ dysfunction. Even in Japan, anti-cancer drug PK/PD clinical research has been conducted across the body organs, with reports on the usefulness of PK/PD analysis in the proper use of molecularly-targeted therapy. On the other hand, even though the development of immune checkpoint drugs is progressing rapidly, there is little information on PK/PD analysis, and the search for effective blood concentrations and fluctuation factors can also provide important basic information in the development of combination therapies with other anti-cancer drugs. Though it has been reported that it tends to be less effective in patients with low trough blood levels of nivolumab, with the pharmacokinetic variables being blood albumin levels and the weight of the patient, there are very few of these reports in Japan. Although the association of adverse event occurrences between genetic polymorphisms and pharmacokinetics has been reported, there have been very few reports of careful administration. It is also anticipated that the need for comprehensive analysis as precision medicine will also increase even in genetic polymorphism. There is no guideline for dose adjustment that takes PK/PD and genetic polymorphism into consideration in careful administration cases, and this is a pressing issue in promoting personalized medicine.