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Lu Y, Zhong H, Tang Q, et al. Construction and verification of CYP3A5 gene polymorphisms using a Saccharomyces cerevisiae expression system to predict drug metabolism. Mol Med Rep. 2017;15(4):1593-1600doi: 10.3892/mmr.2017.6214.
Lu, Y., Zhong, H., Tang, Q., Huang, Z., Jing, N., Smith, J., Miao, R., Li, Y., & Yuan, H. (2017). Construction and verification of CYP3A5 gene polymorphisms using a Saccharomyces cerevisiae expression system to predict drug metabolism. Molecular medicine reports, 15(4), 1593-1600. https://doi.org/10.3892/mmr.2017.6214
Lu, Yao, et al. "Construction and verification of CYP3A5 gene polymorphisms using a Saccharomyces cerevisiae expression system to predict drug metabolism." Molecular medicine reports vol. 15,4 (2017): 1593-1600. doi: https://doi.org/10.3892/mmr.2017.6214
Lu Y, Zhong H, Tang Q, Huang Z, Jing N, Smith J, Miao R, Li Y, Yuan H. Construction and verification of CYP3A5 gene polymorphisms using a Saccharomyces cerevisiae expression system to predict drug metabolism. Mol Med Rep. 2017 Apr;15(4):1593-1600. doi: 10.3892/mmr.2017.6214. Epub 2017 Feb 17. PMID: 28259948; PMCID: PMC5364972.
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Mol Med Rep. 2017 Apr;15(4):1593-1600. doi: 10.3892/mmr.2017.6214. Epub 2017 Feb 17.

Construction and verification of CYP3A5 gene polymorphisms using a Saccharomyces cerevisiae expression system to predict drug metabolism.

Molecular medicine reports

Yao Lu, Hua Zhong, Qing Tang, Zhijun Huang, Ningning Jing, Julie Smith, Rujia Miao, Yapei Li, Hong Yuan

Affiliations

  1. Department of Clinical Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.
  2. Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.
  3. School of Community Health Sciences, University of Nevada, Reno, NV 89557, USA.

PMID: 28259948 PMCID: PMC5364972 DOI: 10.3892/mmr.2017.6214

Abstract

The present study evaluated the ability of a Saccharomyces cerevisiae expression system to predict the pharmacokinetic (PK) activity of a calcium channel blocker in patients with distinct cytochrome P450 3A5 (CYP3A5) polymorphisms. The blood pressure lowering activity of amlodipine in 57 hypertensive patients with CYP3A5*1/*1, CYP3A5*1/*3, CYP3A5*4 and CYP3A5*6 polymorphisms was evaluated by the current study. Subsequently, a Saccharomyces cerevisiae expression system for CYP3A5 gene polymorphisms was constructed to examine the PK activity of CYP3A5*1/*1, CYP3A5*4 and CYP3A5*6 polymorphisms. This system was used to predict the PK of amlodipine and was compared with the in vivo data from different gene polymorphism groups. The blood pressure lowering activity of amlodipine in hypertensive patients varied among CYP3A5 polymorphisms. The in vivo results demonstrated that CYP3A5*6 exhibited the highest metabolic rate, followed by CYP3A5*1/*1, CYP3A5*4 and CYP3A5*1/*3. The difference between CYP3A5*6 and CYP3A5*1/*1 was not statistically significant (P=0.5). In accordance with in vivo data, CYP3A5*1/*1 exhibited the highest in vitro metabolic rate, followed by CYP3A5*6 and CYP3A5*4. With the exception of the comparison between CYP3A5*6 and CYP3A5*1/*1, polymorphisms exhibited statistically significant differences compared with CYP3A5*1/*1 (P<0.05). The Saccharomyces cerevisiae expression system may be a cost effective and potentially useful tool for assessing the PK activity of drugs that are metabolized by CYP3A5.

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