D Maroeska Wm Te Loo, Veroniek Harbers, Lars Vermeltfoort, Marieke Jh Coenen
{"title":"Influence of genetic variants on the pharmacokinetics and pharmacodynamics of sirolimus: a systematic review.","authors":"D Maroeska Wm Te Loo, Veroniek Harbers, Lars Vermeltfoort, Marieke Jh Coenen","doi":"10.2217/pgs-2022-0147","DOIUrl":null,"url":null,"abstract":"<p><p>Sirolimus is an antiproliferative and immunosuppressive compound inhibiting the mTOR pathway, which is often activated in congenital low-flow vascular malformations. Studies have demonstrated the efficacy of sirolimus for this disease. Studies in kidney transplant patients suggest that genetic variants can influence these pharmacokinetic parameters. Therefore, a systematic literature search was performed to gain insight into pharmacogenetic studies with sirolimus. Most studies investigated <i>CYP3A4</i> and <i>CYP3A5</i>, with inconsistent results. No pharmacogenetic studies focusing on sirolimus have been performed for low-flow vascular malformations. We analyzed two common variants of <i>CYP3A4</i> and <i>CYP3A5</i> (<i>CYP3A4*22</i> and <i>CYP3A5*3</i>, respectively) in patients (n = 59) with congenital low-flow vascular malformations treated with sirolimus. No association with treatment outcome was identified in this small cohort of patients.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":"24 11","pages":"629-639"},"PeriodicalIF":1.9000,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacogenomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2217/pgs-2022-0147","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/8/8 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 1
Abstract
Sirolimus is an antiproliferative and immunosuppressive compound inhibiting the mTOR pathway, which is often activated in congenital low-flow vascular malformations. Studies have demonstrated the efficacy of sirolimus for this disease. Studies in kidney transplant patients suggest that genetic variants can influence these pharmacokinetic parameters. Therefore, a systematic literature search was performed to gain insight into pharmacogenetic studies with sirolimus. Most studies investigated CYP3A4 and CYP3A5, with inconsistent results. No pharmacogenetic studies focusing on sirolimus have been performed for low-flow vascular malformations. We analyzed two common variants of CYP3A4 and CYP3A5 (CYP3A4*22 and CYP3A5*3, respectively) in patients (n = 59) with congenital low-flow vascular malformations treated with sirolimus. No association with treatment outcome was identified in this small cohort of patients.
期刊介绍：
Pharmacogenomics (ISSN 1462-2416) is a peer-reviewed journal presenting reviews and reports by the researchers and decision-makers closely involved in this rapidly developing area. Key objectives are to provide the community with an essential resource for keeping abreast of the latest developments in all areas of this exciting field.
Pharmacogenomics is the leading source of commentary and analysis, bringing you the highest quality expert analyses from corporate and academic opinion leaders in the field.
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