Journal
XENOBIOTICA
Volume 46, Issue 8, Pages 677-682Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/00498254.2015.1117159
Keywords
Cyclosporine; CYP 3A; herb-drug interaction; P-glycoprotein; rhubarb
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Funding
- Ministry of Science and Technology, R.O.C. [NSC 102-2320-B-039-014-MY2, MOST 103-2320-B-039 -025, MOST 103-2314-B-039-035-MY3]
- China Medical University, Taichung, Taiwan, R.O.C. [CMU 103-N-01]
- China Medical University Hospital, Taichung, Taiwan, R.O.C. [DMR-104-092, DMR-104-093]
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1. Rhubarb, rhizome of Rheum palmatum L. (RP), is an important herb in clinical Chinese medicine. 2. Cyclosporine (CSP) is an immunosuppressant with narrow therapeutic window. The oral bioavailability of CSP was associated with P-glycoprotein (P-gp) and CYP 3A4. CSP was used as a probe substrate to investigate the in vivo modulation effects of RP on P-gp and CYP 3A. 3. Rats were orally administered 2.5 mg/kg of CSP with and without 0.25 and 1.0 g/kg of RP. The blood CSP concentration was determined by a specific monoclonal fluorescence polarization immunoassay. 4. Both dosages of RP significantly decreased the C-max and AUC(0-t) of CSP in rats. Mechanism studies indicated that RP activated the functions of P-gp and CYP 3A. 5. RP ingestion reduced the systemic exposure of CSP through activating P-gp and CYP 3A.
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