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Expert Opin Drug Metab Toxicol. 2017 Nov;13(11):1135-1146. doi: 10.1080/17425255.2017.1391213. Epub 2017 Oct 20.

Pharmacogenomics of triazole antifungal agents: implications for safety, tolerability and efficacy.

Author information

1
a Department of Pharmacy Practice , Butler University College of Pharmacy and Health Sciences , Indianapolis , IN , USA.
2
b Division of Pharmacy Practice and Administration , UMKC School of Pharmacy at MSU , Springfield , MO , USA.

Abstract

Triazole antifungal agents are prescribed to treat invasive fungal infections in neutropenic and non-neutropenic patients. These antifungal agents are substrates and inhibitors of cytochrome P450 (CYP). Genetic polymorphisms in CYP2C9, CYP2C19 and CYP3A5 can lead to large population-specific variations in drug efficacy and safety, optimal dosing, or contribute to drug interactions associated with this class. Areas covered: This manuscript reviews the pharmacogenomics (i.e. the influence of genetics on drug disposition) of triazole antifungal agents related to their CYP-mediated metabolism and summarizes their implications on triazole efficacy, safety, and tolerability. A search of English language original research, and scholarly reviews describing the pharmacogenomics of triazole antifungal agents and their impact on drug efficacy, safety, and tolerability published from 1980 to present was undertaken using PubMed. Expert opinion: Currently studies demonstrating the pharmacogenomic influences on itraconazole, posaconazole and isavuconazole are minimal and limited to their inhibitory effects on CYP3A4 in expressors of CYP3A5 variants. Conversely, there are significant pharmacogenomic considerations for voriconazole because it interacts with several polymorphic CYPs, most notably CYP2C19. Pharmacogenomics of CYP2C9 do not appear to effect fluconazole safety and efficacy. However, genetic polymorphisms may influence its drug interactions but this needs further study.

KEYWORDS:

CYP2C19; CYP2C9; CYP3A4; CYP3A5; Cytochrome P450; fluconazole; isavuconazole; pharmacogenetics; pharmacogenomics; voriconazole

PMID:
29022838
DOI:
10.1080/17425255.2017.1391213
[Indexed for MEDLINE]

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