title: Evaluation of the in vitro/in vivo drug interaction potential of BST204, a purified dry extract of ginseng, and its four bioactive ginsenosides through cytochrome P450 inhibition/induction and UDP-glucuronosyltransferase inhibition.
abstract: We evaluated the potential of BST204, a purified dry extract of ginseng, to inhibit or induce human liver cytochrome P450 enzymes (CYPs) and UDP-glucuronosyltransferases (UGTs) in vitro to assess its safety. In vitro drug interactions of four bioactive ginsenosides of BST204, S-Rg3, R-Rg3, S-Rh2, and R-Rh2, were also evaluated. We demonstrated that BST204 slightly inhibited CYP2C8, CYP2D6, CYP2C9, and CYP2B6 activities with IC50 values of 17.4, 26.8, 31.5, and 49.7μg/mL, respectively. BST204 also weakly inhibited UGT1A1, UGT1A9, and UGT2B7 activities with IC50 values of 14.5, 26.6, and 31.5μg/mL, respectively. The potential inhibition by BST204 of the three UGT activities might be attributable to S-Rg3, at least in part, as its inhibitory pattern was similar to that of BST204. However, BST204 showed no time-dependent inactivation of the nine CYPs studied. In addition, BST204 did not induce CYP1A2, 2B6, or 3A4/5. On the basis of an in vivo interaction studies, our data strongly suggest that BST204 is unlikely to cause clinically significant drug-drug interactions mediated via inhibition or induction of most CYPs or UGTs involved in drug metabolism in vivo. Our findings offer a clearer understanding and possibility to predict drug-drug interactions for the safe use of BST204 in clinical practice.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Yu Fen
authors.initials: YF
authors.lastname: Zheng
authors.affiliation: College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon 420-743, Republic of Korea.
authors.forename: Soo Hyeon
authors.initials: SH
authors.lastname: Bae
authors.affiliation: College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon 420-743, Republic of Korea.
authors.forename: Eu Jin
authors.initials: EJ
authors.lastname: Choi
authors.affiliation: College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon 420-743, Republic of Korea.
authors.forename: Jung Bae
authors.initials: JB
authors.lastname: Park
authors.affiliation: Green Cross Health Science Co., Ltd., Sungnam, Republic of Korea.
authors.forename: Sun Ok
authors.initials: SO
authors.lastname: Kim
authors.affiliation: Green Cross Health Science Co., Ltd., Sungnam, Republic of Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Jang
authors.affiliation: College of Pharmacy, Kyungpook National University, 80 Daehakro, Buk-gu, Daegu 702-701, Republic of Korea.
authors.forename: Gyu Hwan
authors.initials: GH
authors.lastname: Park
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Wan Gyoon
authors.initials: WG
authors.lastname: Shin
authors.affiliation: College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon 420-743, Republic of Korea.
authors.forename: Euichaul
authors.initials: E
authors.lastname: Oh
authors.affiliation: College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon 420-743, Republic of Korea. Electronic address: baesk@catholic.ac.kr.
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Bae
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D036145:Ginsenosides / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry
chemical_list: C504856:BST204 ginseng extract; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D036145:Ginsenosides; D010936:Plant Extracts; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase
keywords: A purified dry extract of ginseng; BST204; CYPs inhibition/induction; Four bioactive ginsenosides; In vitro drug interaction; UGTs inhibition