Abstract
S-1 (TS-1®) is an oral fluoropyrimidine anticancer agent containing tegafur, oteracil, and gimeracil. Sipjeondaebo-tang (SDT) is a traditional oriental herbal medicine that has potential to alleviate chemotherapy-related adverse effects. The aim of the present study was to evaluate the effect of SDT on the pharmacokinetics of S-1. Sprague-Dawley rats were pretreated with a single dose or repeated doses of SDT for seven consecutive days (1200 mg/kg/day). After the completion of pretreatment with SDT, S-1 was orally administered and plasma concentrations of tegafur, its active metabolite 5-FU, and gimeracil were determined by liquid chromatography-tandem mass spectrometry (LC/MS/MS). A population pharmacokinetic model was developed to evaluate the effect of SDT on pharmacokinetics of tegafur and 5-FU. Although a single dose of SDT did not have any significant effect, the absorption rate of tegafur decreased, and the plasma levels of 5-FU reduced significantly in rats pretreated with SDT for seven days in parallel to the decreased gimeracil concentrations. Population pharmacokinetic modeling also showed the enhanced elimination of 5-FU in the SDT-pretreated group. Repeated doses of SDT may inhibit the absorption of gimeracil, an inhibitor of 5-FU metabolism, resulting in enhanced elimination of 5-FU and decrease its plasma level.
Highlights
S-1 (TS-1® ) is a widely used oral anticancer agent for the treatment of gastric cancer, and it consists of tegafur, gimeracil (2-chloro-2,4-dihydroxypyridine), and oteracil potassium [1,2]
To examine the effects of SDT on S-1 pharmacokinetics, SDT was administered as a single dose or multiple doses for seven successive days prior to S-1 administration, and S-1 pharmacokinetics was compared with that in the control-pretreated group
This study evaluated the potential drug-herb interaction between the anticancer agent S-1 and traditional herbal medicine SDT for alleviating chemotherapy-related adverse effects
Summary
S-1 (TS-1® ) is a widely used oral anticancer agent for the treatment of gastric cancer, and it consists of tegafur, gimeracil (2-chloro-2,4-dihydroxypyridine), and oteracil potassium [1,2]. S-1 has been known as an effective adjuvant treatment for patients who have undergone a gastrectomy with extended (D2) lymph node dissection for advanced gastric cancer [4]. S-1 is an effective adjuvant chemotherapy for resected pancreatic cancer compared to standard treatment with gemcitabine [8]. It is considered an important therapeutic option for the management of pancreatic cancer [9]
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