| Title |
Functional assessment of CYP3A4 allelic variants on lidocaine metabolism in vitro
|
|---|---|
| Published in |
Drug Design, Development and Therapy, December 2017
|
| DOI | 10.2147/dddt.s152366 |
| Pubmed ID | |
| Authors |
Ping Fang, Peng-fei Tang, Ren-ai Xu, Xiang Zheng, Jian Wen, Su-su Bao, Jian-ping Cai, Guo-xin Hu |
| Abstract |
Human cytochrome P450 3A4 is the most abundant isoform of P450 enzyme in the liver. It plays an important role in the metabolism of wide variety of xenobiotic and endogenous substrates. So far, there are few reports about the functional characterization of CYP3A4 variants in terms of specific substrates. The aim of this study was to systematically investigate the genetic polymorphisms of 23 CYP3A4 alleles and evaluate their catalytic activities on the metabolism of lidocaine in vitro. The wild-type and 22 CYP3A4 variants were expressed in Spodoptera frugiperda 21 insect cells. Then the insect microsomes were incubated with the CYP3A4-specific substrate lidocaine. Reactions were performed with 50-3,000 µM for 60 min at 37°C. Lidocaine and its metabolite monoethylglycinexylidide were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry system. Of the 23 CYP3A4 allelic variants tested, 2 variants (CYP3A4*17 and CYP3A4*30) had no detectable enzyme activity; and 5 variants (CYP3A4*2, CYP3A4*5, CYP3A4*9, CYP3A4*16 and CYP3A4*24) showed significantly decreased intrinsic clearance values compared with wild-type CYP3A4*1. As the first study of all these CYP3A4 alleles for lidocaine metabolism, our results in vitro assessment may provide novel insights into the allele-specific and substrate-specific activity of CYP3A4 and may also offer a reference to the personalized treatment of lidocaine in a clinical setting. |
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 35 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 35 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 7 | 20% |
| Researcher | 6 | 17% |
| Student > Ph. D. Student | 5 | 14% |
| Student > Doctoral Student | 2 | 6% |
| Student > Postgraduate | 2 | 6% |
| Other | 1 | 3% |
| Unknown | 12 | 34% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 7 | 20% |
| Biochemistry, Genetics and Molecular Biology | 6 | 17% |
| Medicine and Dentistry | 4 | 11% |
| Chemical Engineering | 1 | 3% |
| Decision Sciences | 1 | 3% |
| Other | 1 | 3% |
| Unknown | 15 | 43% |
Attention Score in Context
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#22,764,772
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Outputs from Drug Design, Development and Therapy
#1,753
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Outputs of similar age from Drug Design, Development and Therapy
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