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- W4377029264 abstract "<b>Abstract ID 50858</b> <b>Poster Board 173</b> <b>Introduction:</b> Irbesartan, a potent and selective angiotensin II type-1 receptor blocker, is mainly metabolized through oxidation and glucuronide conjugation. Its oxidation is primarily mediated by CYP2C9, and the genetic polymorphism of CYP2C9 significantly affects the pharmacokinetics of irbesartan. This study aimed to establish the physiologically based pharmacokinetic (PBPK) model of irbesartan in different <i>CYP2C9</i> genotypes for individualized pharmacotherapy with irbesartan according to the genotype of CYP2C9. <b>Methods:</b> The irbesartan PBPK model was established using PK-Sim<sup>®</sup> in three different CYP2C9 genotypes (<i>CYP2C9*1/*1, *1/*3, and *1/*13</i>). Our pharmacogenomic data of irbesartan and a total of 15 clinical pharmacokinetic data of irbesartan with different demographic characteristics and dose regimens were leveraged to develop and validate the model. Physicochemical and ADME properties of irbesartan were obtained from previously reported data or optimized to capture the plasma concentration-time profiles in different <i>CYP2C9</i> genotypes. <b>Results:</b> Predicted plasma concentration-time profiles were visually similar to the observed profiles in different <i>CYP2C9</i> genotypes. The ranges of fold errors for AUC<sub>inf</sub> and C<sub>max </sub>in development were 1.01-1.09 and 0.92-1.02 respectively, which were strictly satisfied with the evaluation criterion. The ranges of fold errors for AUC<sub>inf</sub> and C<sub>max</sub> in single-dose validation were 0.53-1.87 and 0.61-1.90, respectively, and in multiple-dose validation were 0.87-1.64 and 0.77-1.82, respectively, which were also within the evaluation criterion. <b>Conclusion:</b> The PBPK model of irbesartan developed in this study can be used to predict the pharmacokinetics of irbesartan and for individualized pharmacotherapy with irbesartan in individuals of various races, ages, and CYP2D6 genotypes." @default.
- W4377029264 created "2023-05-19" @default.
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- W4377029264 date "2023-05-18" @default.
- W4377029264 modified "2023-09-29" @default.
- W4377029264 title "Physiologically Based Pharmacokinetic (PBPK) Modeling to Predict the Pharmacokinetics of Irbesartan in Different<i>CYP2C9</i>Genotypes" @default.
- W4377029264 doi "https://doi.org/10.1124/jpet.122.508580" @default.
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