title: Rhubarb decreased the systemic exposure of cyclosporine, a probe substrate of P-glycoprotein and CYP 3A.
abstract: 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 Cmax and AUC0-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.
authors.affiliation: a School of Chinese Medicine, China Medical University , Taichung , Taiwan, R.O.C. .
authors.forename: Chung-Ping
authors.initials: CP
authors.lastname: Yu
authors.affiliation: a School of Chinese Medicine, China Medical University , Taichung , Taiwan, R.O.C. .|b Department of Ophthalmology , China Medical University Hospital , Taichung , Taiwan, R.O.C. .
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Lin
authors.affiliation: c School of Pharmacy, China Medical University , Taichung , Taiwan, R.O.C. .
authors.forename: Shiuan-Pey
authors.initials: SP
authors.lastname: Lin
authors.affiliation: c School of Pharmacy, China Medical University , Taichung , Taiwan, R.O.C. .
authors.forename: Chi-Sheng
authors.initials: CS
authors.lastname: Shia
authors.affiliation: d Graduate Institute of Pharmaceutical Chemistry, China Medical University , Taichung , Taiwan, R.O.C. , and.
authors.forename: Pei-Hua
authors.initials: PH
authors.lastname: Chang
authors.affiliation: c School of Pharmacy, China Medical University , Taichung , Taiwan, R.O.C. .|e Department of Pharmacy , China Medical University Hospital , Taichung , Taiwan, R.O.C.
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Hou
authors.affiliation: c School of Pharmacy, China Medical University , Taichung , Taiwan, R.O.C. .|e Department of Pharmacy , China Medical University Hospital , Taichung , Taiwan, R.O.C.
authors.forename: Yo-Wen
authors.initials: YW
authors.lastname: Hsieh
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051381:Rats; D012250:Rheum / Q000737:chemistry*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004365:Drugs, Chinese Herbal; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D051544:Cytochrome P-450 CYP3A
keywords: CYP 3A; Cyclosporine; P-glycoprotein; herb–drug interaction; rhubarb