Effect of several Chinese natural health products of human cytochrome P450 metabolism.
OBJECTIVE
Traditional Chinese medicines (TCM) are believed by many to be safe and used for self-medication without supervision. Although the risk appears to be low, certain TCM have been associated with a number of serious adverse reactions. A preliminary study was undertaken with 12 products using a human cytochrome P450 (CYP450) isozyme assay to determine if these products could affect human drug metabolism.


METHODS
Aliquots of samples were analyzed directly or as extracts for their potential to affect CYP450 2C9, 2C19, 2D6, and 3A4 mediated-metabolism of marker substrates using an in vitro fluorometric microtiter plate assay.


RESULTS
One product was found to be a Chinese Proprietary Medicine (CPM). Most aqueous extracts inhibited CYP450 mediated-metabolism of at least 3 isozymes (ranging from 25-100%). All liquid samples markedly inhibited the metabolism of all 4 isozymes. De le ke chuan kang and Rensheng dao were the strongest CYP450 inhibitors.


CONCLUSIONS
Our in vitro findings demonstrate that TCM can inhibit CYP450 2C9, 2C19, 2D6 and 3A4 mediated-metabolism. TCM need to be examined further under clinical settings to determine if potential interactions will occur that affect the safety and efficacy of conventional therapeutic products.
Office of Science, Therapeutic Products Directorate, Health Canada, Ottawa, Ontario, Canada; Centre for Research in Biopharmaceuticals, University of Ottawa, Ontario, K1A 1B6 Canada. brian_foster@hc-sc.gc.ca
Brian C
BC
Foster
Susan
S
Vandenhoek
Rainy
R
Tang
Jason W
JW
Budzinski
Anthony
A
Krantis
K Y
KY
Li
D001189:Aryl Hydrocarbon Hydroxylases; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006801:Humans; D008516:Medicine, Chinese Traditional; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010946:Plants, Medicinal / Q000737:chemistry; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors / Q000378:metabolism
D065690:Cytochrome P-450 CYP2D6 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D004365:Drugs, Chinese Herbal; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; C104464:CYP3A protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; D039181:Steroid 16-alpha-Hydroxylase