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Research ArticleArticle

Predicting stereo-selective disposition of carvedilol in adult and pediatric chronic heart failure patients by incorporating pathophysiological changes in organ blood flows - A physiologically based pharmacokinetic approach

Muhammad Fawad Rasool, Feras Khalil and Stephanie Laer
Drug Metabolism and Disposition April 11, 2016, dmd.115.068858; DOI: https://doi.org/10.1124/dmd.115.068858
Muhammad Fawad Rasool
Institute of Clinical Pharmacy and Pharmacotherapy, University of Dusseldorf
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  • For correspondence: fawadrasool@bzu.edu.pk
Feras Khalil
Institute of Clinical Pharmacy and Pharmacotherapy, University of Dusseldorf
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Stephanie Laer
Institute of Clinical Pharmacy and Pharmacotherapy, University of Dusseldorf
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Data Supplement

Files in this Data Supplement:

  • Supplemental Data -

    Supplemental Methods

    Supplemental Table 1 - Comparison of area under the systemic drug concentration-time curve from time zero to infinity (AUC0-∞) and area under the systemic drug concentration-time curve from time zero to last measured concentration (AUC last)

    Supplemental Figure 1 - Sensitivity analysis on various model input parameters and their effect on predicted oral clearance (CL/F) and area under the curve (AUC0-∞) of R and S carvedilol in pediatric chronic heart failure patients

    Supplemental Figure 2 - Predicted R and S-carvedilol systemic concentration vs. time profiles from the sensitivity analysis by changing the values of input parameters in 10 runs

    Supplemental Figure 3 - Observed vs. predicted concentrations plots in healthy adults after intravenous (A, B), and oral (C, D) racemic carvedilol application, and in chronic heart failure patients after oral application racemic carvedilol (E, F)

    Supplemental Figure 4 - Model predictions in the entire pediatric age range n=15 (0.12 to 17.8 year) including the young adult n=1 (19.3 year) after administering 0.09 mg/kg racemic carvedilol, (A, B) systemic concentration-time plots...

    Supplemental Figure 5 - Observed vs. predicted concentrations plots in pediatric CHF patients after administering 0.09 mg/kg racemic carvedilol (a, b).

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