Publication: Pharmaceutics
Abstract
Torsemide, a diuretic used for cardiovascular and chronic disease, shows inter-individual pharmacokinetic variability that had not been linked to specific genetic factors. This study built a population pharmacokinetic model from serum concentrations in 112 healthy Korean males using Phoenix NLME (cross-validated with NONMEM), examining CYP2C9 and OATP1B1 genetic polymorphisms as covariates. Both CYP2C9 and OATP1B1 phenotypes significantly affected torsemide pharmacokinetic parameters, with differences in clearance of 36.5-51% by CYP2C9 phenotype and differences in volume of distribution of 41-64.6% by OATP1B1 phenotype, together improving the model's ability to explain inter-individual variability. These findings suggest that CYP2C9 and OATP1B1 genotyping could inform more individualized torsemide dosing in the future.
Author(s): Jeong SH, Jang JH, Cho HY, Lee YB
Published: 2022 年 4 月 1 日
Phoenix NLME：Two Genes, Better Predictions
Phoenix NLME's population model, cross-validated with NONMEM, showed two genetic polymorphisms together meaningfully improve torsemide exposure predictions in this study. Within a Phoenix platform used across more than 170 academic institutions, Phoenix NLME is also available through RsNLME, bringing population PK/PD modeling into R for teams who prefer that environment.
