Abstract | PURPOSE: METHODS: Parameters associated with the plasma concentrations of bisoprolol at steady-state were analyzed in 61 patients (mean age 66.21 ± 9.49 years; mean total body weight 8.90 ± 12.26 kg) with CHF using non-linear mixed-effect modeling (NONMEM). A validation set of 17 patients with heart failure was used to estimate the predictive performance of the pharmacokinetic model. RESULTS: The typical mean value for bisoprolol clearance (CL), estimated by the base model (without covariates), in our population was 11.4 l h(-1). In the full model, covariates such as bisoprolol total daily dose (DD) and creatinine clearance were included. The final regression model for the clearance of bisoprolol was the following: CL (l h(-1)) = 4.68 + 0.859 * DD. CONCLUSION: The derived PK model describes the clearance of bisoprolol in patients with CHF, showing that the total daily dose of bisoprolol is the most important covariate. This finding will provide the basis for future PK studies on beta blockers in this specific patient population and lead to better overall management of heart failure.
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Authors | Valentina N Nikolic, Tatjana Jevtovic-Stoimenov, Radmila Velickovic-Radovanović, Stevan Ilic, Marina Deljanin-Ilic, Dragan Marinkovic, Svetlana Apostolović, Dragana Stanojevic, Slavoljub Zivanovic, Nikola Stefanovic, Srdjan Pesic, Dejana Ruzic Zecevic, Jasmina R Milovanovic, Slobodan M Jankovic |
Journal | European journal of clinical pharmacology
(Eur J Clin Pharmacol)
Vol. 69
Issue 4
Pg. 859-65
(Apr 2013)
ISSN: 1432-1041 [Electronic] Germany |
PMID | 23093041
(Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adrenergic beta-1 Receptor Antagonists
- Bisoprolol
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Topics |
- Adrenergic beta-1 Receptor Antagonists
(administration & dosage, pharmacokinetics, therapeutic use)
- Adult
- Aged
- Aged, 80 and over
- Bisoprolol
(administration & dosage, pharmacokinetics, therapeutic use)
- Chronic Disease
- Female
- Heart Failure
(blood, drug therapy)
- Humans
- Male
- Metabolic Clearance Rate
- Middle Aged
- Models, Biological
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