Sunday, July 23, 2017

The Roles of CYP2C19 and CYP3A4 in Voriconazole Pharmacogenetics

Voriconazole is a triazole antifungal agent used to treat serious fungal infections. It is primarily used in immunocompromised patients, such as those undergoing organ transplantation. CYP2C19 is the primary enzyme responsible for voriconazole metabolism. CYP3A4, CYP3A5 and CYP2C9 also play a role, secondary to CYP2C19. The influence of genetic polymorphisms in CYP2C19 is well documented in clinical studies, and the Clinical Pharmacogenetics Implementation Consortium (CPIC) recently released guideline for voriconazole dosing based on CYP2C19 genotype.

In the August issue of Clinical Pharmacology and Therapeutics, Gautier-Veyret et al wrote a perspective piece discussing two retrospective studies showing that genetic variations in CYP3A4 gene may influence voriconazole trough concentrations, suggesting that in addition to CYP2C19, CYP3A4 should also be genotyped for voriconazole dosing.

In response to this, CPIC guideline authors Walsh et al acknowledged the different opinions on the role of CYP3A4 in voriconazole pharmacokinetics and clarified the reasons why CPIC authors feel there is NOT sufficient evidence to recommend altered voriconazole dosing based on genetic polymorphisms in CYP3A4/CYP3A5.

For further details see both articles in the August edition of Clinical Pharmacology and Therapeutics:

Walsh TJ, Moriyama B, Penzak SR, Klein TE, Caudle KE.
Clin Pharmacol Ther. 2017 Aug;102(2):190. doi: 10.1002/cpt.681. Epub 2017 Apr 29. 
PMID: 28455946

Gautier-Veyret E, Fonrose X, Stanke-Labesque F.
Clin Pharmacol Ther. 2017 Aug;102(2):189. doi: 10.1002/cpt.662. Epub 2017 May 26. 
Post a Comment