Population Pharmacokinetic Analysis of Bisoprolol in Patients with Stable Coronary Artery Disease
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Abstract
Background and objectives
Bisoprolol is a selective beta adrenergic antagonist commonly used in treatment of coronary artery disease (CAD). The aim of our analysis was to estimate and identify different factors that could affect bisoprolol clearance (CL) and develop a population pharmacokinetic model in patients with stable coronary artery disease (CAD).
Methods
Population pharmacokinetic analysis was performed by using sixty-six plasma concentrations from the same number of patients (mean age 60.26 ± 9.68 years; mean total body weight 80.37 ± 12.93 kg) with CAD. We examined the effects of various clinical and demographic parameters using nonlinear mixed-effect modeling (NONMEM) with ADVAN1 with TRANS2 subroutine. The pharmacokinetics of bisoprolol in patients with CAD were suitably defined by an oral one-compartment model.
Results
The typical mean value for bisoprolol CL, estimated by the base model, in the target population was 6.76 l/h. The only demographic covariate which affected bisoprolol pharmacokinetic variability was creatinine clearance (CLcr). The final model of bisoprolol clearance was described by following equation: CL (l/h) = 2.83 + 0.0385 × CLcr (ml/min). Validation of the final model was performed in a group of 17 patients using the validation set and bootstrapping analysis.
Conclusions
These findings suggest that one of the causes of clearance of bisoprolol variability in patients with CAD is the difference in renal function.
Notes
Acknowledgements
This study was partially financially supported by Grants No 175007 and No III 41018 given by the Serbian Ministry of Education, Science and Technological Development. The authors declare that they have no conflict of interest.
Compliance with Ethical Standards
Funding
This study was partially financially supported by Grants No 175007 and No III 41018 given by the Serbian Ministry of Education, Science and Technological Development.
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent
Informed consent was obtained from all individual participants included in the study.
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