Correlation of CYP2C19 genotype with plasma voriconazole levels: a preliminary retrospective study in Indians

Abstract

Voriconazole is an antifungal drug essentially metabolized by cytochrome P450 (CYP2C19) isozyme. Plasma voriconazole levels exhibit wide inter-individual variability due to several factors like age, weight, food or drug interactions or CYP2C19 polymorphisms. In the present study, we assessed the correlation of voriconazole levels with CYP2C19 genotype in patients on voriconazole therapy. Biochemistry Department of a 480 inpatient bed tertiary care hospital in India. Plasma voriconazole estimation was done in seventy-two patients on standard weight based voriconazole therapy by High Performance Liquid Chromatography (HPLC) while genotype assessment for the CYP2C19*2 and *3 was done by PCR-RFLP and *17 by ARMS-PCR. Statistical analysis and genotype-phenotype correlation was done by comparing the drug levels with the CYP2C19 genotype. CYP2C19 polymorphisms influence voriconazole metabolism. A wide variability is seen in plasma levels with only 51% attaining therapeutic levels. The allele frequency of *2, *3 and *17 variant were found to be 33.3, 0.7 and 18% respectively. The drug levels in carriers of *2 allele (poor metabolizers) was twofold higher than that in extensive metabolizers. However, the influence of *2 allele was compromised in presence of *17 allele and patients had low voriconazole levels. In addition to the genotype, co-medication and clinical condition remarkably influenced voriconazole concentration. Plasma voriconazole levels are influenced by CYP2C19 variants, drug interactions and clinical condition of the patient. Genotype assessment at initiation of therapy followed by drug monitoring would help optimizing therapeutic efficacy and minimizing toxicity.