2. Academic Validation
  3. Kinetics of cytochrome P450 enzymes for metabolism of sodium tanshinone IIA sulfonate in vitro

Kinetics of cytochrome P450 enzymes for metabolism of sodium tanshinone IIA sulfonate in vitro

  • Chin Med. 2016 Mar 22;11:11. doi: 10.1186/s13020-016-0083-z.
Dong-Sheng Ouyang 1,  Wei-Hua Huang 2,  Dan Chen 2,  Wei Zhang 2,  Zhi-Rong Tan 2,  Jing-Bo Peng 2,  Yi-Cheng Wang 3,  Ying Guo 3,  Dong-Li Hu 3,  Jian Xiao 4,  Yao Chen 1
Affiliations

Affiliations

  • 1 Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 110 Xiangya Road, Changsha, 410078 Hunan China ; Institute of Clinical Pharmacology, Central South University, 110 Xiangya Road, Changsha, 410078 Hunan China.
  • 2 Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 110 Xiangya Road, Changsha, 410078 Hunan China.
  • 3 Institute of Clinical Pharmacology, Central South University, 110 Xiangya Road, Changsha, 410078 Hunan China.
  • 4 Department of Pharmacy, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan China.
PMID: 27006687 DOI: 10.1186/s13020-016-0083-z
Abstract

Background: Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA for treating cardiovascular disorders. The roles of Cytochrome P450 enzymes (CYPs) in the metabolism of STS have remained unclear. This study aims to screen the main CYPs for metabolism of STS and study their interactions in vitro.

Methods: Seven major CYPs were screened for metabolism of STS by human liver microsomes (HLMs) or recombinant CYP isoforms. Phenacetin (CYP1A2), coumarin (CYP2A6), tolbutamide (CYP2C9), metoprolol (CYP2D6), chlorzoxazone (CYP2E1), S-mephenytoin (CYP2C19), and midazolam (CYP3A4) were used as probe substrates to determine the potential of STS in affecting CYP-mediated phase I metabolism in humans. Enzyme kinetic studies were performed to investigate the modes of inhibition of the enzyme-substrate interactions by GraphPad Prism Enzyme Kinetic 5 Demo software.

Results: Sodium tanshinone IIA sulfonate inhibited the activity of CYP3A4 in a dose-dependent manner by the HLMs and CYP3A4 isoform. The K m and V max values of STS were 54.8 ± 14.6 µM and 0.9 ± 0.1 nmol/mg protein/min, respectively, for the HLMs and 7.5 ± 1.4 µM and 6.8 ± 0.3 nmol/nmol P450/min, respectively, for CYP3A4. CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1, and CYP2C19 showed minimal or no effects on the metabolism of STS.

Conclusion: This in vitro study showed that STS mainly inhibited the activities of CYP3A4.

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