Comparison of the pharmacokinetics of S-1, an oral anticancer agent, in Western and Japanese patients.Report as inadecuate




Comparison of the pharmacokinetics of S-1, an oral anticancer agent, in Western and Japanese patients. - Download this document for free, or read online. Document in PDF available to download.

* Corresponding author 1 Department of Pharmacy 2 Modèles et méthodes de l-évaluation thérapeutique des maladies chroniques 3 Taiho Pharmaceutical Co, Ltd. 4 Department of Gastrointestinal Medical Oncology and Digestion Diseases 5 Centre René Gauducheau 6 NDDO Oncology

Abstract : OBJECTIVE: S-1 is an oral anticancer agent combining tegafur FT, a prodrug of 5-fluorouracil 5-FU, with potassium oxonate oteracil and gimeracil CDHP respectively to mitigate gastrointestinal toxicity and increase the half-life of 5-FU. This article presents a population pharmacokinetic analysis of these four compounds in Western cancer patients. The second objective was to compare the pharmacokinetics of S-1 in Western and Japanese patients. METHODS: A single dose 25-45 mg-m2 of S-1 was administered to 60 patients. In each patient, 6 concentrations of FT, 5-FU, oteracil and CDHP were measured over 24 hr. Using NONMEM, oteracil and CDHP were analyzed separately, and the individual estimates of CDHP parameters were included in the joint analysis of FT and 5-FU. We used validation techniques to assess differences between the two populations, and finally we compared the exposures in Western and Japanese patients using simulations. RESULTS: A compartmental model describing the PK of the 4 compounds was developed. The influence of CDHP on the elimination of 5-FU was well described by an enzymatic inhibition model. The model provided a good fit for all compounds. The pharmacokinetics for 5-FU and oteracil were similar between Western and Japanese patients, but apparent differences in exposure to 5-FU resulted from different total doses due to different body sizes.

Keywords : 5-FU oral anticancer drug population pharmacokinetics model validation ethnic differences





Author: Emmanuelle Comets - Kazumasa Ikeda - Paulo Hoff - Pierre Fumoleau - Jantien Wanders - Yusuke Tanigawara -

Source: https://hal.archives-ouvertes.fr/



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