Development of a pharmacokinetic model to optimize the dosage regimen of TS-1, a combination preparation of tegafur, gimeracil and oteracil potassium.

Saori Inoue, Hisakazu Ohtani, Masayuki Tsujimoto, Satoko Hori, Yasufumi Sawada

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

BACKGROUND: TS-1 is a combination preparation of tegafur, a prodrug of 5-fluorouracil (5-FU), with gimeracil, a potent inhibitor of dihydropyrimidine dehydrogenase (DPD), which mediates the inactivation of 5-FU. UFT is a combination preparation of tegafur with uracil, which also inhibits DPD, though less potently; UFT has a higher content of tegafur than that in TS-1. We aimed to develop a pharmacokinetic model to describe the kinetics of tegafur and 5-FU after the administration of TS-1 and UFT. METHODS: We developed a model incorporating the inhibition of DPD by gimeracil and uracil, and fitted the model to the observed kinetics of tegafur and 5-FU after the administration of TS-1 and UFT. Then, we simulated the plasma 5-FU profiles in patients with renal dysfunction and those after replacement of TS-1 with UFT and compared them with the observed profiles. RESULTS: The developed model could appropriately describe the plasma concentration profiles of 5-FU and tegafur after the administration of TS-1 in patients with normal and impaired renal function. CONCLUSION: The developed model may be useful to optimize the dosage regimen of TS-1 under various clinical conditions.

Original languageEnglish
Pages (from-to)162-168
Number of pages7
JournalDrug Metabolism And Pharmacokinetics
Volume22
Issue number3
DOIs
Publication statusPublished - 2007 Jun
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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