title: Potential modulation on P-glycoprotein and CYP3A by soymilk and miso: in vivo and ex-vivo studies.
abstract: P-glycoprotein (P-gp) and CYP3A4 both play very important roles in drug bioavailability, resistance and interactions. Our in vitro studies indicated that P-gp function was activated by many isoflavones. This study investigated the in vivo effects of soymilk and miso, isoflavone-rich soy foods, on P-gp and CYP3A by tracing the pharmacokinetics of cyclosporine (CSP), a probe drug of P-gp. Rats were orally administered CSP with and without soymilk or miso. A specific monoclonal fluorescence polarisation immunoassay was used to determine the blood concentration of CSP. The results showed that soymilk and miso significantly decreased the C(max) of CSP by 64.5% and 78.3%, and reduced the AUC(0-540) by 64.9% and 78.3%, respectively. Mechanism studies revealed that the activities of P-gp and CYP3A4 were induced by soymilk and miso. In conclusion, ingestion of soymilk and miso significantly activated the functions of P-gp and CYP3A.
authors.affiliation: School of Pharmacy, China Medical University, Taichung 404, Taiwan, ROC.
authors.forename: C P
authors.initials: CP
authors.lastname: Yu
authors.forename: Y W
authors.initials: YW
authors.lastname: Hsieh
authors.forename: S P
authors.initials: SP
authors.lastname: Lin
authors.forename: Y C
authors.initials: YC
authors.lastname: Chi
authors.forename: P
authors.initials: P
authors.lastname: Hariharan
authors.forename: P D L
authors.initials: PD
authors.lastname: Chao
authors.forename: Y C
authors.initials: YC
authors.lastname: Hou
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D045730:Soy Foods / Q000032:analysis*; D041942:Soy Milk / Q000737:chemistry / Q000378:metabolism*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D051544:Cytochrome P-450 CYP3A
keywords: CYP3A; Cyclosporine; Miso; P-gp; Soymilk powders