期刊
JOURNAL OF FOOD AND DRUG ANALYSIS
卷 26, 期 -, 页码 S125-S132出版社
FOOD & DRUG ADMINSTRATION
DOI: 10.1016/j.jfda.2017.11.005
关键词
Cyclosporine; P-glycoprotein; Cytochrome P450 3A; Herb-drug interactions; Pharmacokinetics
资金
- Ministry of Science and Technology, Taipei, Taiwan [MOST 105-2314-B-039-018, MOST 106-2320-B-039-009]
- China Medical University Hospital, Taichung, Taiwan [DMR-105-101, DMR-106-138, DMR-106-139]
Coptidis Rhizoma (CR), the rhizome of Coptis chinensis FRANCH, is a popular Chinese herb. CR contains plenty of isoquinoline alkaloids such as berberine, coptisine and palmatine. Cyclosporine (CSP), an important immunosuppressant with narrow therapeutic window, is employed as a probe substrate of P-glycoprotein (P-gp) and CYP3A4 in order to investigate the in vivo modulation effect of CR on P-gp and CYP3A4. Three groups of rats were orally administered CSP without and with single dose or repeated dosing of CR in a parallel design. Blood samples were collected at specific time points and the blood CSP concentration was determined by a specific monoclonal fluorescence polarization immunoassay. The results showed that a single dose (1.0 g/kg) and the 7th dose (1.0 g/kg) of CR significantly decreased the C-max of CSP by 56.9% and 70.4%, and reduced the AUC(0-540) by 56.4% and 68.7%, respectively. Cell study indicated that CR decoction, berberine, coptisine, palmatine all activated the efflux transport of P-gp. Ex-vivo study showed that the serum metabolites of CR activated CYP 3A4. In conclusion, through using CSP as an in vivo probe substrate, we have verified that oral intake of CR activated the functions of P-gp and CYP3A based on in vivo and in vitro studies. Copyright (C) 2017, Food and Drug Administration, Taiwan. Published by Elsevier Taiwan LLC.
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