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Bisoprolol pharmacokinetics and body composition in patients with chronic heart failure: a longitudinal study

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

We investigated bisoprolol pharmacokinetics, including longitudinal changes and importance of patient characteristics in chronic heart failure.

Methods

Forty-six patients with chronic heart failure (57 % male, NYHA class I/II/III = 2/36/8) were followed for an average of 8 ± 2 months. At baseline and follow-up, plasma bisoprolol concentrations were determined and body composition was measured using dual-energy X-ray absorptiometry. A bisoprolol pharmacokinetic model was built with non-linear mixed-effects modeling to analyze the association with various parameters of body composition.

Results

Mean bisoprolol clearance (10.2 L/h) was 30 % lower than in healthy individuals and correlated with MDRD4-estimated renal function. The mean volume of distribution (230 L) was similar to healthy population and was associated with total body mass and skeletal muscle index (SMI). During follow-up, we observed minor changes in the absorption rate constant (2.83 vs. 2.27 h−1, P = 0.030) and volume of distribution (227 vs. 250 L, P = 0.004), which are not clinically relevant.

Conclusions

In patients with chronic heart failure, bisoprolol clearance was associated with estimated renal function; thus, in moderately and severely decreased renal function, patients may need to have their dose adjusted. Patients with low body weight or low SMI have greater fluctuations and higher maximal plasma concentrations of bisoprolol because of the lower volume of distribution. Longitudinal changes of bisoprolol pharmacokinetics were not associated with changes in body composition.

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Contributions of authors

Katja Cvan Trobec: wrote manuscript, designed research, performed research, analyzed data, provided important intellectual content, approved final version of manuscript

Iztok Grabnar: wrote manuscript, analyzed data, provided important intellectual content, approved final version of manuscript

Mojca Kerec Kos: wrote manuscript, designed research, analyzed data, provided important intellectual content, approved final version of manuscript

Tomaz Vovk: performed research, provided important intellectual content, approved final version of manuscript

Jurij Trontelj: performed research, provided important intellectual content, approved final version of manuscript

Stefan D. Anker: wrote manuscript, provided important intellectual content, approved final version of manuscript

Giuseppe Rosano: wrote manuscript, provided important intellectual content, approved final version of manuscript

Mitja Lainscak: wrote manuscript, designed research, performed research, provided important intellectual content, approved final version of manuscript

Author information

Authors and Affiliations

  1. Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia

    Katja Cvan Trobec, Iztok Grabnar, Mojca Kerec Kos, Tomaz Vovk & Jurij Trontelj

  2. Innovative Clinical Trials, Department of Cardiology and Pneumology, University Medical Center Göttingen (UMG), Göttingen, Germany

    Stefan D. Anker

  3. Centre for Clinical and Basic Research, Department of Medical Sciences, IRCCS San Raffaele Pisana, Rome, Italy

    Giuseppe Rosano

  4. Cardiovascular and Cell Science Research, St George’s University, London, UK

    Giuseppe Rosano

  5. Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

    Mitja Lainscak

  6. Department of Cardiology, General Hospital Celje, SI-3000, Celje, Slovenia

    Mitja Lainscak

Authors
  1. Katja Cvan Trobec
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  2. Iztok Grabnar
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  3. Mojca Kerec Kos
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  4. Tomaz Vovk
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  6. Stefan D. Anker
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  7. Giuseppe Rosano
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  8. Mitja Lainscak
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Corresponding author

Correspondence to Mitja Lainscak.

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The authors declare that they have no conflict of interest.

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Fig. S1

Dependance of the volume of distribution of bisoprolol (L) on body weight and skeletal muscle index (SMI). (GIF 41 kb)

High-resolution image (TIF 187 kb)

Fig. S2

Changes in pharmacokinetic parameters during follow-up (N = 39). (GIF 73 kb)

High-resolution image (TIF 232 kb)

Fig. S3

Individual predicted/observed ratio of bisoprolol apparent clearance versus MDRD4 estimates. Predicted clearance—a priori predictions using the final model; observed clearance—Bayesian estimates using the base model. (JPG 230 kb)

Table S1

(DOC 69 kb)

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Cvan Trobec, K., Grabnar, I., Kerec Kos, M. et al. Bisoprolol pharmacokinetics and body composition in patients with chronic heart failure: a longitudinal study. Eur J Clin Pharmacol 72, 813–822 (2016). https://doi.org/10.1007/s00228-016-2041-1

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  • DOI: https://doi.org/10.1007/s00228-016-2041-1

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