Publication: Frontiers in Pharmacology
Abstract
Voriconazole pharmacokinetics are substantially influenced by CYP2C19 genetic variation, but a joint model characterizing both voriconazole and its N-oxide metabolite alongside genotype-based dose optimization had not been established. This study analyzed 427 plasma concentrations from 78 immunocompromised patients receiving voriconazole to build a joint population pharmacokinetic model using Phoenix NLME, then used Monte Carlo simulation to evaluate dosing across CYP2C19 genotypes. CYP2C19 genetic variation substantially influenced voriconazole pharmacokinetics, and simulations showed the standard maintenance dose would result in subtherapeutic levels for some genotypes, indicating that higher daily doses may be needed for certain patients. The joint model supports genotype-guided voriconazole dose individualization to improve outcomes and reduce toxicity risk in immunocompromised patients.
Author(s): Li S, Wu S, Gong W, Cao P, Chen X, Liu W, Xiang L, Wang Y, Huang J
Published: January 3, 2022
Phoenix NLME: A Joint Parent-Metabolite Model
Phoenix NLME built a joint population model of voriconazole and its metabolite in this study, supporting genotype-guided dose individualization. Within a Phoenix platform built on more than 30 years of PK/PD expertise, Phoenix NLME is also available through RsNLME, bringing population PK/PD modeling into R for teams who prefer that environment.
