A semimechanistic population pharmacokinetic and pharmacodynamic model incorporating autoinduction for the dose justification of TAS-114.

ABSTRACT: TAS-114 is a dual deoxyuridine triphosphatase (dUTPase) and dihydropyrimidine dehydrogenase (DPD) inhibitor expected to widen the therapeutic index of capecitabine. Its maximum tolerated dose (MTD) was determined from a safety perspective in a combination study with capecitabine; however, its inhibitory effects on DPD activity were not assessed in the study. The dose justification to select its MTD as the recommended dose in terms of DPD inhibition has been required, but the autoinduction profile of TAS-114 made it difficult. To this end, an approach using a population pharmacokinetic (PPK)/pharmacodynamic (PD) model incorporating autoinduction was planned; however, the utility of this approach in the dose justification has not been reported. Thus, the aim of this study was to demonstrate

SUBMITTER: Araki H 

PROVIDER: S-EPMC9124359 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature