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Effect of Ginkgo on CYP2C9: In vitro and in vivo studies
Author(s) -
Greenblatt D. J.,
Moltke L. L.,
Perloff E. S.,
Luo Y.,
Harmatz J. S.,
Bedir E.,
Khan I. A.,
Goldman P.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.075
Subject(s) - ginkgo biloba , pharmacology , chemistry , in vivo , amentoflavone , quercetin , microsome , in vitro , cyp2c9 , tolbutamide , biochemistry , cytochrome p450 , medicine , enzyme , biology , antioxidant , microbiology and biotechnology , insulin
Purposes In vitro and clinical studies evaluated the effect of exposure to Ginkgo biloba (GB), or its components, on the activity of human CYP2C9. Methods 29 chemical constituents of GB were isolated, purified (J Agr Food Chem 2002; 50:3150), and tested as inhibitors of human CYP2C9 in vitro, based on flurbiprofen (F) hydroxylation activity in human liver microsomes (JPharm Pharmacol 2004; 56: 1039). Healthy volunteers (n=11) received 100 mg of F on two occasions in a crossover study, preceded by two 120‐mg doses of GB or of matching placebo (P). Results CYP2C9 inhibition in vitro was produced by amentoflavone (IC50=0.035 μM), sesamin (21.2 μM), quercetin (25.8 μM), and 3‐nonadec‐8‐enyl‐benzene‐1,2‐diol (5.6 μM). Ginkgolides, bilobalide, and flavonol aglycones had weak or negligible inhibitory activity. Mean (±SE) clinical kinetic parameters for F when given with P and GB, respectively, were: peak plasma concentration, 12.2±1.0 vs. 11.6±0.8 μg/ml; elimination half‐life, 4.3±0.5 vs. 4.0±0.6 hr; clearance, 31±4 vs. 29±3 ml/min. Differences were not significant. Conclusions Several components of GB_especially amentoflavone_are potentially important inhibitors of CYP2C9. However coadministration of F (an index substrate for CYP2C9) with usual doses of GB in humans had no effect on the kinetics of F. Potential CYP2C9 inhibitors in GB either are not present in sufficient quantities to produce clinically detectable inhibition in vivo, or do not reach the liver at inhibitory concentrations. Clinical Pharmacology & Therapeutics (2005) 77 , P48–P48; doi: 10.1016/j.clpt.2004.12.075