title: Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP 3A.
abstract: Liquorice (root of Glycyrrhiza uralensis FISCH) is an ingredient of candies and used as a popular medicine in Europe and oriental countries. Cyclosporine (CsA), an immunosuppressant with narrow therapeutic window, is widely used in transplant patients. The absorption and disposition of CsA were associated with P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4). This study investigated the effects of liquorice extract (LE) and its major ingredient, glycyrrhizin (GZ), on CsA pharmacokinetics in rats. The results indicated that LE and GZ significantly decreased the peak blood concentration and the areas under the curves of CsA in rats. Mechanism studies revealed that glycyrrhetic acid (GA), the major metabolite of GZ, significantly activated the functions of P-gp and CYP3A4. In conclusion, liquorice significantly reduced the oral bioavailability of CsA through activating P-gp and CYP3A4.
authors.affiliation: School of Pharmacy, China Medical University, Taichung 40402, Taiwan, ROC. hou5133@gmail.com
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Hou
authors.forename: Shiuan-Pey
authors.initials: SP
authors.lastname: Lin
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*; D000818:Animals; D001682:Biological Availability; D045744:Cell Line, Tumor; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D006035:Glycyrrhiza / Q000737:chemistry*; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D041743:Herb-Drug Interactions; D006801:Humans; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D010936:Plant Extracts; D019695:Glycyrrhizic Acid; D016572:Cyclosporine; D003577:Cytochrome P-450 Enzyme System; C465260:Cyp3a2 protein, rat; D051544:Cytochrome P-450 CYP3A