Construction and verification of CYP3A5 gene polymorphisms using a Saccharomyces cerevisiae expression system to predict drug metabolism
| Autor: | Yapei Li, Yao Lu, Hong Yuan, Qing Tang, Julie Smith, Zhijun Huang, Ning-ning Jing, Hua Zhong, Rujia Miao |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Cancer Research
gene polymorphism medicine.drug_class Saccharomyces cerevisiae Calcium channel blocker 030204 cardiovascular system & hematology Pharmacology Biology Biochemistry 03 medical and health sciences 0302 clinical medicine Pharmacokinetics pharmacodynamics Genetics medicine Cytochrome P-450 CYP3A Humans Amlodipine pharmacokinetic CYP3A5 Molecular Biology Antihypertensive Agents Polymorphism Genetic Base Sequence Models Genetic cytochrome P450 3A5 Oncogene Reproducibility of Results Articles Molecular medicine Recombinant Proteins drug metabolism Oncology 030220 oncology & carcinogenesis Cancer research Molecular Medicine Gene polymorphism Drug metabolism medicine.drug |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| DOI: | 10.3892/mmr.2017.6214 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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