title: Bisoprolol pharmacokinetics and body composition in patients with chronic heart failure: a longitudinal study.
abstract: OBJECTIVE
  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.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Katja
authors.initials: K
authors.lastname: Cvan Trobec
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Iztok
authors.initials: I
authors.lastname: Grabnar
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Mojca
authors.initials: M
authors.lastname: Kerec Kos
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Tomaz
authors.initials: T
authors.lastname: Vovk
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Jurij
authors.initials: J
authors.lastname: Trontelj
authors.affiliation: Innovative Clinical Trials, Department of Cardiology and Pneumology, University Medical Center Göttingen (UMG), Göttingen, Germany.
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.affiliation: Centre for Clinical and Basic Research, Department of Medical Sciences, IRCCS San Raffaele Pisana, Rome, Italy.|Cardiovascular and Cell Science Research, St George's University, London, UK.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rosano
authors.affiliation: Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. mitja.lainscak@guest.arnes.si.|Department of Cardiology, General Hospital Celje, SI-3000, Celje, Slovenia. mitja.lainscak@guest.arnes.si.
authors.forename: Mitja
authors.initials: M
authors.lastname: Lainscak
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000097:blood / Q000493:pharmacokinetics*; D000368:Aged; D000369:Aged, 80 and over; D017298:Bisoprolol / Q000097:blood / Q000493:pharmacokinetics*; D001823:Body Composition; D002908:Chronic Disease; D005260:Female; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000502:physiology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D017298:Bisoprolol
keywords: Bisoprolol; Body composition; Cachexia; Chronic heart failure; Pharmacokinetics