CYP3A4/5 combined genotype analysis for predicting statin dose requirement for optimal lipid control.

Drug Metabolism and Drug Interactions Pub Date : 2013-01-01 DOI:10.1515/dmdi-2012-0031

Joseph Paul Kitzmiller, Danielle M Sullivan, Mitchell A Phelps, Danxin Wang, Wolfgang Sadee

{"title":"CYP3A4/5 combined genotype analysis for predicting statin dose requirement for optimal lipid control.","authors":"Joseph Paul Kitzmiller, Danielle M Sullivan, Mitchell A Phelps, Danxin Wang, Wolfgang Sadee","doi":"10.1515/dmdi-2012-0031","DOIUrl":null,"url":null,"abstract":"Background: Statins are indicated for prevention of atherosclerotic cardiovascular disease. Metabolism of certain statins involves the cytochrome P450 3A (CYP3A) enzymes, and CYP3A4*22 significantly influences the dose needed for achieving optimal lipid control for atorvastatin, simvastatin, and lovastatin. CYP3A4/5 combined genotype approaches have proved useful in some studies involving CYP3A substrates. We intend to compare a combined genotype analysis to our previously reported single gene CYP3A4 analysis.Methods: A total of 235 patients receiving stable statin doses were genotyped and grouped by CYP3A4/5 status.Results: The number and demographic composition of the patients categorized into the combined genotype groups were consistent with those reported for other cohorts. Dose requirement was significantly associated with the ordered combined-genotype grouping; median daily doses were nearly 40% greater for CYP3A4/5 intermediate metabolizers compared with poor metabolizers, and median daily doses were nearly double for extensive metabolizers compared with poor metabolizers. The combined-genotype approach, however, did not improve the genotype-dosage correlation p-values when compared with the previously-reported analysis; values changed from 0.129 to 0.166, 0.036 to 0.185, and 0.014 to 0.044 for atorvastatin, simvastatin, and the combined statin analysis, respectively.Conclusions: The previously-reported single-gene approach was superior for predicting statin dose requirement in this cohort.","PeriodicalId":11319,"journal":{"name":"Drug Metabolism and Drug Interactions","volume":"28 1","pages":"59-63"},"PeriodicalIF":0.0000,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/dmdi-2012-0031","citationCount":"21","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Metabolism and Drug Interactions","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1515/dmdi-2012-0031","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}

引用次数: 21

Abstract

Background: Statins are indicated for prevention of atherosclerotic cardiovascular disease. Metabolism of certain statins involves the cytochrome P450 3A (CYP3A) enzymes, and CYP3A4*22 significantly influences the dose needed for achieving optimal lipid control for atorvastatin, simvastatin, and lovastatin. CYP3A4/5 combined genotype approaches have proved useful in some studies involving CYP3A substrates. We intend to compare a combined genotype analysis to our previously reported single gene CYP3A4 analysis.

Methods: A total of 235 patients receiving stable statin doses were genotyped and grouped by CYP3A4/5 status.

Results: The number and demographic composition of the patients categorized into the combined genotype groups were consistent with those reported for other cohorts. Dose requirement was significantly associated with the ordered combined-genotype grouping; median daily doses were nearly 40% greater for CYP3A4/5 intermediate metabolizers compared with poor metabolizers, and median daily doses were nearly double for extensive metabolizers compared with poor metabolizers. The combined-genotype approach, however, did not improve the genotype-dosage correlation p-values when compared with the previously-reported analysis; values changed from 0.129 to 0.166, 0.036 to 0.185, and 0.014 to 0.044 for atorvastatin, simvastatin, and the combined statin analysis, respectively.

Conclusions: The previously-reported single-gene approach was superior for predicting statin dose requirement in this cohort.

查看原文本刊更多论文

CYP3A4/5联合基因型分析预测最佳脂质控制所需他汀类药物剂量。

背景:他汀类药物可用于预防动脉粥样硬化性心血管疾病。某些他汀类药物的代谢涉及细胞色素P450 3A (CYP3A)酶，CYP3A4*22显著影响阿托伐他汀、辛伐他汀和洛伐他汀实现最佳脂质控制所需的剂量。CYP3A4/5联合基因型方法已被证明在一些涉及CYP3A底物的研究中是有用的。我们打算将联合基因型分析与我们之前报道的单基因CYP3A4分析进行比较。方法:对235例接受稳定剂量他汀类药物治疗的患者按CYP3A4/5状态进行基因分型和分组。结果:合并基因型组患者的数量和人口统计学组成与其他队列的报道一致。剂量需要量与有序组合基因型分组显著相关;CYP3A4/5中间代谢物的中位日剂量比差代谢物高出近40%，广泛代谢物的中位日剂量比差代谢物高出近一倍。然而，与先前报道的分析相比，联合基因型方法并没有提高基因型与剂量的相关性p值;阿托伐他汀、辛伐他汀和联合他汀分析的值分别为0.129 ~ 0.166、0.036 ~ 0.185和0.014 ~ 0.044。结论:在该队列中，先前报道的单基因方法在预测他汀类药物剂量需求方面优于其他方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Drug Metabolism and Drug Interactions

自引率

0.00%

发文量