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Molecules 2017, 22(9), 1488; doi:10.3390/molecules22091488

Effect of Sipjeondaebo-Tang on the Pharmacokinetics of S-1, an Anticancer Agent, in Rats Evaluated by Population Pharmacokinetic Modeling

1
Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA
2
College of Pharmacy, Wonkwang University, Iksan, Jeonbuk 54538, Korea
3
College of Pharmacy, Catholic University of Daegu, 13-13 Hayang-ro, Hayang-eup, Gyeongsan-si, Gyeongbuk 38430, Korea
4
School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, Korea
5
Department of Rehabilitation Medicine, School of Medicine, Catholic University of Daegu, Daegu 42472, Korea
Tae Hwan Kim and Soyoung Shin contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 9 July 2017 / Revised: 31 August 2017 / Accepted: 5 September 2017 / Published: 7 September 2017
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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. View Full-Text
Keywords: herbal medicine; drug-drug interaction; pharmacokinetics; 5-FU; gimeracil; Sipjeondaebo-tang herbal medicine; drug-drug interaction; pharmacokinetics; 5-FU; gimeracil; Sipjeondaebo-tang
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MDPI and ACS Style

Kim, T.H.; Shin, S.; Shin, J.C.; Bulitta, J.B.; Weon, K.-Y.; Yoo, S.D.; Park, G.-Y.; Jeong, S.W.; Kwon, D.R.; Min, B.S.; Woo, M.H.; Shin, B.S. Effect of Sipjeondaebo-Tang on the Pharmacokinetics of S-1, an Anticancer Agent, in Rats Evaluated by Population Pharmacokinetic Modeling. Molecules 2017, 22, 1488.

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