title: Quercetin and rutin reduced the bioavailability of cyclosporine from Neoral, an immunosuppressant, through activating P-glycoprotein and CYP 3A4.
abstract: Quercetin and rutin are popular flavonoids in plant foods, herbs, and dietary supplements. Cyclosporine (CSP), an immunosuppressant with a narrow therapeutic window, is a substrate of P-glycoprotein (P-gp) and cytochrome P-450 3A4 (CYP3A4). This study investigated the effects of quercetin and rutin on CSP pharmacokinetics from Neoral and relevant mechanisms. Rats were orally administered Neoral with and without quercetin or rutin. The blood CSP concentration was assayed by a specific monoclonal fluorescence polarization immunoassay. The results showed that quercetin and rutin significantly decreased the C(max) of CSP by 67.8 and 63.2% and reduced the AUC(0-540) by 43.3 and 57.2%, respectively. The in vitro studies indicated that the quercetin and rutin induced the functions of P-gp and CYP3A4. In conclusion, quercetin and rutin decreased the bioavailability of CSP through activating P-gp and CYP3A. Transplant patients treated with Neoral should avoid concurrent consumption of quercetin or rutin to minimize the risk of allograft rejection.
authors.affiliation: School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan, Republic of China.
authors.forename: Chung-Ping
authors.initials: CP
authors.lastname: Yu
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Wu
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Hou
authors.forename: Shiuan-Pey
authors.initials: SP
authors.lastname: Lin
authors.forename: Shang-Yuan
authors.initials: SY
authors.lastname: Tsai
authors.forename: Chiung-Tong
authors.initials: CT
authors.lastname: Chen
authors.forename: Pei-Dawn Lee
authors.initials: PD
authors.lastname: Chao
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism*; D004336:Drug Antagonism; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D011794:Quercetin / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012431:Rutin / Q000008:administration & dosage*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D012431:Rutin; D016572:Cyclosporine; D011794:Quercetin; D051544:Cytochrome P-450 CYP3A