Effects of Cytochrome P450 (CYP) 2C19 Genetic Polymorphisms on Voriconazole Serum Levels: A Report of Two Cases

Abstract

Voriconazole (VCZ), a triazole antifungal, is the first-line drug used in the treatment of invasive aspergillosis. Voriconazole is primarily metabolized by the enzyme cytochrome P450 (CYP) 2C19. Genetic polymorphisms of CYP2C19 have been reported to be associated with variability in VCZ pharmacokinetics that may lead to a decrease in its efficacy. In this report, we describe two patients who were treated by VCZ for presumed invasive pulmonary aspergillosis, who had CYP2C19*1/*17 genotypes and whose target serum levels could not be reached despite the appropriate dose of VCZ given. Trough serum levels of VCZ were measured on the 5th day of VCZ treatment which was reported as 0.2 mg/l for the first patient, and 0.1 mg/l for the second patient. We suspected that the patients may be an ultrarapid or rapid metabolizer of VCZ, and genotyping for CYP2C19 was performed. The CYP2C19*1/*17 genotype was detected in two of the patients which predicted phenotype of rapid metabolizer for CYP2C19 activity. To the best of our knowledge, these patients are the first cases reported to have very low plasma levels of VCZ associated with CYP2C19 genetic variant alleles in Turkey. CYP2C19 genotyping may potentially improve the safety and efficacy of VCZ treatment.

Keywords

• voriconazole
• polymorphism
• cytochrome p450
• invasive fungal disease