Pharmacogenomic Profiling of Voriconazole Enables Predicting Its Toxicity in Pediatric Leukemia and Hematopoietic Stem Cell Transplant Recipients.

CYP2C19 genotype–voriconazole plasma level–hepatotoxicity correlation in a North Indian pediatric population

In a prospective cohort of 102 North Indian pediatric patients (mean age 6.56 years) receiving voriconazole for leukemia/HSCT, CYP2C19 genotype significantly correlated with plasma levels: poor metabolizers (*2/*2) had the highest concentrations (8.73 µg/mL), rapid metabolizers had subtherapeutic levels (1.65 µg/mL), with only 52.9% of levels in the therapeutic range. Hepatotoxicity occurred in 28.4% and was significantly associated with supratherapeutic levels. Genotype and dose were the key determinants of drug exposure in multivariate analysis, supporting genotype-guided dosing with therapeutic drug monitoring.

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This study provides pharmacogenomic data for an underrepresented population: South Asian pediatric patients receiving voriconazole. With hepatotoxicity in 28.4% of cases — frequently associated with supratherapeutic levels in poor metabolizers — the case for preemptive CYP2C19 genotyping before voriconazole initiation in children is strong.

Clinical impact : 2/3 · Evidence strength : 2/3 · Novelty : 1/2 · Sample size : 1/1 · Journal quality : 1/1 → Total : 7/10