Inflammation-driven variability in drug metabolism: Insights from voriconazole treatment of HSCT recipients

Combined effect of *CYP2C19* genotype and inflammation (CRP ≥ 10 mg/L) on voriconazole exposure, with inflammation driving phenoconversion toward slower metabolism

This retrospective study of 126 hematopoietic stem cell transplant recipients analyzes the joint effect of CYP2C19 genotype and inflammation (CRP) on voriconazole exposure. Both CYP2C19-predicted phenotype and CRP are associated with dose-corrected trough concentrations (p < 2e-16), with inflammation increasing supra-therapeutic and reducing subtherapeutic levels. The effect is most pronounced in intermediate and rapid metabolizers (33% vs 3% supra-therapeutic concentrations under inflammation). In a longitudinal subset, concentrations track inflammatory status over time. The authors recommend intensified therapeutic drug monitoring coupled with concurrent CRP assessment.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

This study is an elegant clinical demonstration of inflammation-driven phenoconversion: CYP2C19 genotype alone is insufficient to predict exposure when CRP rises. Integrating CRP into voriconazole therapeutic monitoring is directly applicable and especially relevant in transplant recipients, where inflammation is frequent. A concrete reminder that pharmacogenetic phenotype is dynamic, not fixed.