Bayesian Population Pharmacokinetic Modeling of Eltrombopag in Chronic Hepatitis C Patients

Bayesian Population Pharmacokinetic Modeling of Eltrombopag in Chronic Hepatitis C Patients Background and Objectives Eltrombopag is a thrombopoietic growth factor that is approved for the treatment of throm- bocytopenia in chronic hepatitis C virus (HCV) patients. We aimed to describe eltrombopag population pharmacokinetics in hepatitis C patients. Bayesian statistical approach will be applied to screen for patients’ characteristics associated with eltrombopag pharmacokinetic parameters. Methods A population pharmacokinetic analysis was conducted using WinBUGS version 1.4.3. Data from 483 individuals with chronic HCV infection were analyzed. This analysis is a secondary analysis of two clinical studies (ENABLE1 and ENABLE2) sponsored by GlaxoSmithKline. Several patients’ characteristics were examined as possible covariates of the population pharmacokinetic model. Prior information from previous studies was incorporated in the bayesian model as prior distribution to estimate pharmacokinetic parameters. Results A two-compartment pharmacokinetic model with first-order absorption with exponential error model best fit the data. We identified East Asian race and total bilirubin level as predictors of eltrombopag clearance. Typical value for distributional clearance was 0.762 L/h (95% Bayesian credible set, 0.703–0.826), for volume of distribution of the central and peripheral compartments were 12 L (10.9–13.4) and 10.9 L (10.4–11.5), and for absorption lag time was 0.947 h (0.918–0.977). Assum- ing an average total bilirubin of 21.7 µmol/L, the typical elimination clearance value http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of of Drug Metabolism and Pharmacokinetics Springer Journals

Bayesian Population Pharmacokinetic Modeling of Eltrombopag in Chronic Hepatitis C Patients

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Publisher
Springer Journals
Copyright
Copyright © 2018 by Springer International Publishing AG, part of Springer Nature
Subject
Biomedicine; Pharmacology/Toxicology; Pharmacy; Human Physiology; Pharmaceutical Sciences/Technology; Medical Biochemistry
ISSN
0378-7966
eISSN
2107-0180
D.O.I.
10.1007/s13318-018-0490-x
Publisher site
See Article on Publisher Site

Abstract

Background and Objectives Eltrombopag is a thrombopoietic growth factor that is approved for the treatment of throm- bocytopenia in chronic hepatitis C virus (HCV) patients. We aimed to describe eltrombopag population pharmacokinetics in hepatitis C patients. Bayesian statistical approach will be applied to screen for patients’ characteristics associated with eltrombopag pharmacokinetic parameters. Methods A population pharmacokinetic analysis was conducted using WinBUGS version 1.4.3. Data from 483 individuals with chronic HCV infection were analyzed. This analysis is a secondary analysis of two clinical studies (ENABLE1 and ENABLE2) sponsored by GlaxoSmithKline. Several patients’ characteristics were examined as possible covariates of the population pharmacokinetic model. Prior information from previous studies was incorporated in the bayesian model as prior distribution to estimate pharmacokinetic parameters. Results A two-compartment pharmacokinetic model with first-order absorption with exponential error model best fit the data. We identified East Asian race and total bilirubin level as predictors of eltrombopag clearance. Typical value for distributional clearance was 0.762 L/h (95% Bayesian credible set, 0.703–0.826), for volume of distribution of the central and peripheral compartments were 12 L (10.9–13.4) and 10.9 L (10.4–11.5), and for absorption lag time was 0.947 h (0.918–0.977). Assum- ing an average total bilirubin of 21.7 µmol/L, the typical elimination clearance value

Journal

European Journal of of Drug Metabolism and PharmacokineticsSpringer Journals

Published: Jun 14, 2018

References

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