Publication: British Journal of Clinical Pharmacology
Abstract
CYP2C19 polymorphisms are known to affect voriconazole plasma concentrations, but the extent of this effect relative to other factors, and its relationship to adverse reactions, remained under-explored in children. This study in 60 Japanese pediatric patients treated with voriconazole examined the occurrence of cholestasis and thrombocytopenia, using previously modeled population pharmacokinetic estimates (with missing values estimated via Bayesian methods in Phoenix NLME) alongside CYP2C19 genotyping. Patients experiencing adverse reactions had significantly higher voriconazole concentrations, with a trend toward higher levels in CYP2C19*2/*3 carriers, and a predictive model incorporating genotype, CRP, and platelet count improved prediction of adverse reactions. The findings underscore a role for CYP2C19 polymorphism in voriconazole-induced thrombocytopenia and cholestasis in children.
Author(s): Hikino K, Shoji K, Saito J, Fukunaga K, Liu X, Matsui T, Utano T, Takebayashi A, Tomizawa D, Kato M, Matsumoto K, Ishikawa T, Kawai T, Nakamura H, Miyairi I, Terao C, Mushiroda T
Published: 2025 年 2 月 25 日
Phoenix NLME：Bayesian Estimates for Missing Data
Phoenix NLME's Bayesian estimation filled in missing concentration data for this pediatric voriconazole study, helping link genotype and exposure to adverse reactions. Phoenix NLME is the engine behind population PK/PD modeling, combining the flexibility of code with the ease of a guided interface, part of a Phoenix platform that centralizes data, analyses, and templates with built-in collaboration.
