title: Modulation of Hepatic Cytochrome P450 Enzymes by Curcumin and its Pharmacokinetic Consequences in Sprague-dawley Rats.
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.
  
  
  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 μM. 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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  CUR can inhibit the in vitro CYP3A-mediated metabolism of TES in RLM. 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.
authors.affiliation: New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 701-310, Republic of Korea.
authors.forename: Sang-Bum
authors.initials: SB
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 534-729, Republic of Korea.
authors.forename: Seung-Sik
authors.initials: SS
authors.lastname: Cho
authors.affiliation: Department of Pharmacy, College of Pharmacy, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Hyun-Jong
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Department of Pharmacy, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 534-729, Republic of Korea.
authors.forename: In-Soo
authors.initials: IS
authors.lastname: Yoon
keywords: Buspirone; curcumin; cytochrome P450; hepatic metabolism; rat