Discordant CYP2C19 genotype-phenotype relationship in voriconazole metabolism: impact of inflammation on drug exposure in a Chinese patient.
TL;DR
A case of a 49-year-old Chinese woman with essential thrombocythaemia who was treated with voriconazole for possible invasive pulmonary aspergillosis, who required unusually high doses to achieve therapeutic voriconazole concentrations without apparent adverse effects under therapeutic drug monitoring (TDM).
Abstract
Voriconazole is commonly used for the treatment of invasive aspergillosis. Its metabolism is influenced by pharmacogenetic polymorphisms of CYP2C19 as well as by inflammatory states. We report a case of a 49-year-old Chinese woman with essential thrombocythaemia who was treated with voriconazole for possible invasive pulmonary aspergillosis. Despite possessing a CYP2C19 *1/*1 normal metaboliser genotype, she required unusually high doses (14.5 mg/kg/day), nearly twice the standard dose, to achieve therapeutic voriconazole concentrations without apparent adverse effects under therapeutic drug monitoring (TDM). Notably, increased C-reactive protein (CRP) levels are associated with decreased CYP2C19 activity and can inform cautious dose titration. Although pharmacogenetics plays an important role in voriconazole metabolism, this report highlights the lack of correlation between genotype and clinical pharmacokinetics, as reflected by TDM results.