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

Katja Cvan Trobec, Iztok Grabnar, Mojca Kerec Kos, Tomaz Vovk, Jurij Trontelj, Stefan D. Anker, Giuseppe Rosano, Mitja Lainscak

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalEuropean Journal of Clinical Pharmacology
DOIs
Publication statusAccepted/In press - Mar 21 2016

Keywords

  • Bisoprolol
  • Body composition
  • Cachexia
  • Chronic heart failure
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

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