Modulation of hepatic cytochrome p450 enzymes by curcumin and its pharmacokinetic consequences in sprague-dawley rats

Sang-Bum Kim; Seung-Sik Cho; Hyun-Jong Cho; In-Soo Yoon

Articles

Abstract

Pharmacognosy Magazine,2015,11,44s3,s580-s584.

DOI:10.4103/0973-1296.172965

Published:December 2015

Type:Original Article

Authors:

Author(s) affiliations:

Sang-Bum Kim¹, Seung-Sik Cho², Hyun-Jong Cho³, In-Soo Yoon²
¹ New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 701 310, Korea
² Department of Pharmacy, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 534 729, Korea
³ Department of Pharmacy, College of Pharmacy, Kangwon National University, Chuncheon 200 701, Korea

Abstract:

Background: Curcumin (CUR) is a polyphenolic component derived from an herbal remedy and dietary spice turmeric (Curcuma longa). Objective: The aim of this study was to investigate inhibitory effects of CUR on in vitro cytochrome P450 (CYP) activity and in vivo pharmacokinetic consequences of single CUR dose in rats. Materials and Methods: An in vitro CYP inhibition study in rat liver microsomes (RLM) was conducted using probe substrates for CYPs. Then, an in vivo pharmacokinetics of intravenous buspirone (BUS), a probe substrate for CYP3A, was studied with the concurrent administration of oral CUR in rats. Results: In the in vitro CYP inhibition study, CUR inhibited the CYP3A-mediated metabolism of testosterone (TES) with a half maximal inhibitory concentration of 11.0 ΁ 3.3 mM. However, the impact of a single oral CUR dose on the pharmacokinetics of BUS in rats is limited, showing that CUR cannot function as an inhibitor for CYP3A-mediated drug metabolism in vivo. Conclusion: To the best of our knowledge, our results are the first reported data regarding the inhibition of in vitro CYP3A-mediated metabolism of TES and the in vivo impact of a single CUR dose on the pharmacokinetics of BUS in rats. Further study is required to draw a confirmative conclusion on whether CUR can be a clinically relevant CYP3A4 inhibitor.