Abstract
Herb-drug interactions have received more attention in recent years because of the widespread popularity of herbal supplements. However, there are limited data on the effect of herbs on glucuronidation in humans. The goal of this work was to examine the effect of Ginkgo biloba extract and its main flavonoid and terpene lactone constituents on mycophenolic acid (MPA) 7-O-glucuronidation. Human liver (HLM) and intestinal (HIM) microsomes were incubated with MPA and G. biloba extract (unhydrolyzed or acid-hydrolyzed), quercetin, kaempferol, ginkgolide A, ginkgolide B, or bilobalide. MPA-7-O-glucuronide formation was inhibited in HLM and HIM incubations by unhydrolyzed [IC50 = 84.3 (HLM) and 6.9 (HIM) μg/ml] and hydrolyzed [IC50 = 20.9 (HLM) and 4.3 (HIM) μg/ml] G. biloba extracts, quercetin [IC50 = 19.1 (HLM) and 5.8 (HIM) μM], and kaempferol [IC50 = 23.1 (HLM) and 7.7 (HIM) μM]. Terpene lactones did not show inhibition of MPA glucuronidation. Quercetin was a mixed-type inhibitor in HLM and HIM incubations [Ki = 11.3 (HLM) and 2.8 (HLM) μM], whereas kaempferol was a noncompetitive inhibitor in HLM (Ki = 33.7 μM) and a mixed-type inhibitor in HIM (Ki = 4.5 μM). These results indicate that G. biloba extract or quercetin- and kaempferol-rich supplements may inhibit intestinal and hepatic glucuronidation of MPA. Future studies are needed to evaluate the clinical significance of this interaction.
Footnotes
-
Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
doi:10.1124/dmd.109.030080.
-
- UGT
- UDP glucuronosyltransferase
- MPA
- mycophenolic acid
- MPAG
- mycophenolic acid-7-O-glucuronide
- HLM
- human liver microsome(s)
- HIM
- human intestinal microsome(s)
- UDPGA
- UDP-glucuronic acid.
- Received August 31, 2009.
- Accepted November 3, 2009.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
DMD articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|