title: Sodium tanshinone IIA sulfonate and its interactions with human CYP450s.
abstract: 1.Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA, a famous Chinese medicine used for many years to treat cardiovascular disorders. However, the role of cytochrome P450 (CYP) enzymes in the metabolism of STS was unclear. In this study, we screened the main CYPs for the metabolism of STS and studied their interactions in vitro. 2.Seven CYPs were screened for the metabolism of STS by human liver microsomes (HLMs) or recombinant CYP isoforms. To determine the potential of STS to affect CYP-mediated phase I metabolism in humans, phenacetin (CYP1A2), coumarin (CYP2A6), tolbutamide (CYP2C9), metoprolol (CYP2D6), chlorzoxazone (CYP2E1), S-Mephenytoin (CYP2C19), and midazolam (CYP3A4) were used as the respective probe substrates. Enzyme kinetic studies were performed to investigate the mode of inhibition of the enzyme-substrate interactions. 3.STS inhibited the activity of CYP3A4 in a dose-dependent manner in the HLMs and CYP3A4 isoform. Other CYP isoforms, including CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1, and CYP2C19, showed minimal or no effect on the metabolism of STS. 4.The results suggested that STS primarily inhibits the activities of CYP3A4 in vitro, and STS has the potential to perpetrate drug-drug interactions with other CYP3A4 substrates.
authors.affiliation: a Department of Clinical Pharmacology , Xiangya Hospital, Central South University , Changsha , Hunan , China and.
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.affiliation: a Department of Clinical Pharmacology , Xiangya Hospital, Central South University , Changsha , Hunan , China and.
authors.forename: X-X
authors.initials: XX
authors.lastname: Lin
authors.affiliation: a Department of Clinical Pharmacology , Xiangya Hospital, Central South University , Changsha , Hunan , China and.
authors.forename: W-H
authors.initials: WH
authors.lastname: Huang
authors.affiliation: a Department of Clinical Pharmacology , Xiangya Hospital, Central South University , Changsha , Hunan , China and.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.affiliation: a Department of Clinical Pharmacology , Xiangya Hospital, Central South University , Changsha , Hunan , China and.
authors.forename: Z-R
authors.initials: ZR
authors.lastname: Tan
authors.affiliation: a Department of Clinical Pharmacology , Xiangya Hospital, Central South University , Changsha , Hunan , China and.
authors.forename: J-B
authors.initials: JB
authors.lastname: Peng
authors.affiliation: b Institute of Clinical Pharmacology, Central South University , Changsha , Hunan , China.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Wang
authors.affiliation: b Institute of Clinical Pharmacology, Central South University , Changsha , Hunan , China.
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
authors.affiliation: b Institute of Clinical Pharmacology, Central South University , Changsha , Hunan , China.
authors.forename: D-L
authors.initials: DL
authors.lastname: Hu
authors.affiliation: a Department of Clinical Pharmacology , Xiangya Hospital, Central South University , Changsha , Hunan , China and.|b Institute of Clinical Pharmacology, Central South University , Changsha , Hunan , China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
mesh_terms: D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology*
chemical_list: D004365:Drugs, Chinese Herbal; D010616:Phenanthrenes; C024894:tanshinone II A sodium sulfonate; D003577:Cytochrome P-450 Enzyme System
keywords: CYP3A4; Chinese medicine; drug–drug interaction; sodium tanshinone IIA sulfonate