期刊
DRUG METABOLISM AND PHARMACOKINETICS
卷 26, 期 2, 页码 154-161出版社
JAPANESE SOC STUDY XENOBIOTICS
DOI: 10.2133/dmpk.DMPK-10-RG-107
关键词
herb-drug interaction; cytochromes P450; CYP3A4; mechanism-based inhibitor; Phyllanthus amarus; phyllanthin; hypophyllanthin
资金
- Thai Traditional Medicine Development Foundation
- Office of the Higher Education Commission
- National Research Council of Thailand
- Khon Kaen University, Thailand
- Thailand Research Fund [PHD/0118/2549]
- Nitsupa Wattanachai [PHD/0167/2548]
- Wichittra Tassaneeyakul
Phyllanthus amarus has long been used as a herbal medicine in several countries. Phytochemicals in herbal medicine may interact with cytochromes P450 (CYP) and thus raise the potential of herb-drug interactions: therefore, the inhibitory effects of P. amarus and its major phytochemicals phyllanthin and hypophyllanthin on CYP isoforms were determined using human liver microsomes and selective substrates. Both ethanolic and aqueous extracts of P. amarus inhibited CYP1A2, CYP2D6, CYP2E1 and CYP3A4 in a dose-dependent manner. Compared to known CYP3A inhibitors, the IC50 values of the ethanolic and aqueous extracts on testosterone 6 beta-hydroxylation were higher than that of ketoconazole but were lower than those of erythromycin and clarithromycin. Both extracts were weak inhibitors of CYP1A2, CYP2D6 and CYP2E1. In addition, phyllanthin and hypophyllanthin were potent mechanism-based inhibitors of CYP3A4 with K-I values of 1.75 +/- 1.20 mu M and 2.24 +/- 1.84 mu M and k(inact) values of 0.18 +/- 0.05 min(-1) and 0.15 +/- 0.06 min(-1), respectively. The k(inact)/K-I ratios of these lignans were higher than those reported for some therapeutic drugs that act as mechanism-based inhibitors of CYP3A4. These results suggest that co-administration of P. amarus with drugs that are metabolized by CYP3A4 may potentially result in herb-drug interactions.
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