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Effects of epigallocatechin gallate on the oral bioavailability and pharmacokinetics of tamoxifen and its main metabolite, 4-hydroxytamoxifen, in rats

Shin, Sang-Chula; Choi, Jun-Shikb

doi: 10.1097/CAD.0b013e32832d6834
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The effects of epigallocatechin gallate (EGCG) on the oral bioavailability and pharmacokinetics of tamoxifen and its metabolite, 4-hydroxytamoxifen, were investigated in rats. A single dose of tamoxifen was administered intravenously (2 mg/kg) and orally (10 mg/kg) with or without epigallocatechin (0.5, 3 and 10 mg/kg) to rats. The presence of EGCG significantly altered the pharmacokinetics of orally administered tamoxifen. Compared with the oral control group (given tamoxifen alone), the area under the plasma concentration–time curve and the peak plasma concentration of tamoxifen significantly (P<0.05 for 3 mg/kg of EGCG, P<0.01 for 10 mg/kg of EGCG) increased 48.4–77.0 and 57.1–89.7%, respectively. Consequently, the absolute bioavailability of tamoxifen in the presence of EGCG (3 and 10 mg/kg) was 48.9–78.1%, which was significantly enhanced (P<0.05 for 3 mg/kg of EGCG, P<0.01 for 10 mg/kg of EGCG) compared with the oral control group (23.7%). Moreover, the relative bioavailability of tamoxifen was 1.48–1.77-fold greater than that of the control group. EGCG at a dose of 10 mg/kg significantly increased the area under the plasma concentration–time curve (P<0.05, 40.3%) of 4-hydroxytamoxifen, but the metabolite–parent ratio of 4-hydroxytamoxifen was also significantly altered (P<0.05 for 10 mg/kg of EGCG), implying that the formation of 4-hydroxytamoxifen was considerably affected by EGCG. The increase in bioavailability of tamoxifen is likely to be due to the decrease in first-pass metabolism in the intestine and liver by inhibition of P-glycoprotein and CYP3A by EGCG. The increase in oral bioavailability of tamoxifen in the presence of EGCG should be taken into consideration of potential drug interactions between tamoxifen and EGCG.

aCollege of Pharmacy, Chonnam National University

bBK21 Team, College of Pharmacy, Chosun University, Gwangju, Republic of Korea

Correspondence to Jun-Shik Choi, PhD, College of Pharmacy, Chosun University, Dong-Gu, Gwangju 501-759, Republic of Korea

Tel: +86 62 230 6365; fax: +86 62 222 5414; e-mail: jsachoi@chosun.ac.kr

Received 5 March 2009 Revised form accepted 27 April 2009

© 2009 Lippincott Williams & Wilkins, Inc.