Interpersonal Factors in the Pharmacokinetics and Pharmacodynamics of Voriconazole: Are CYP2C19 Genotypes Enough for Us to Make a Clinical Decision?

Background: Invasive mycoses are serious infections with high mortality and increasing incidence. Voriconazole, an important drug to treat invasive mycosis, is metabolized mainly by the cytochrome P450 family 2 subfamily C member 19 enzyme (CYP2C19) and is affected by the genotypes of CYP2C19. Objective: We reviewed studies on how genotypes affect the pharmacokinetics and pharmacodynamics of voriconazole, and attempted to determine a method to decide on dosage adjustments based on genotypes, after which, the main characteristic of voriconazole was clarified in details. The pharmacokinetics of voriconazole are influenced by various inter and intrapersonal factors, and for certain populations, such as geriatric patients and pediatric patients, these influences must be considered. CYP2C19 genotype represents the main part of the interpersonal variability related to voriconazole blood concentrations. Thus monitoring the concentration of voriconazole is needed in clinical scenarios to minimize the negative influences of inter and intrapersonal factors. Several studies provided evidence on the stable trough concentration range from 1-2 to 4-6 mg/L, which was combined to consider the efficacy and toxicity. However, the therapeutic drug concentration needs to be narrowed down and evaluated by large-scale clinical trials. Conclusion: Though there is insufficient evidence on the relationship between CYP2C19 genotypes and clinical outcomes, there is a great potential for the initial voriconazole dose selection to be guided by the CYP2C19 genotype. Finally, voriconazole therapeutic drug monitoring is essential to provide patient-specific dosing recommendations, leading to more effective anti-fungal regimens to increase clinical efficacy and reduce adverse drug reactions. Keywords: Voriconazole, pharmacogenomics, pharmacokinetics, CYP2C19 polymorphisms, therapeutic drug monitoring, genotype guided dosing.