title: Population pharmacokinetics of bisoprolol in patients with chronic heart failure.
abstract: OBJECTIVE
  The aim of the study was to develop a population pharmacokinetic (PK) model for clearance of bisoprolol in patients with congestive heart failure (CHF).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pharmacology Department, Medical Faculty, University of Nis, Nis, Serbia. valentina@medfak.ni.ac.rs
authors.forename: Valentina N
authors.initials: VN
authors.lastname: Nikolic
authors.forename: Tatjana
authors.initials: T
authors.lastname: Jevtovic-Stoimenov
authors.forename: Radmila
authors.initials: R
authors.lastname: Velickovic-Radovanović
authors.forename: Stevan
authors.initials: S
authors.lastname: Ilic
authors.forename: Marina
authors.initials: M
authors.lastname: Deljanin-Ilic
authors.forename: Dragan
authors.initials: D
authors.lastname: Marinkovic
authors.forename: Svetlana
authors.initials: S
authors.lastname: Apostolović
authors.forename: Dragana
authors.initials: D
authors.lastname: Stanojevic
authors.forename: Slavoljub
authors.initials: S
authors.lastname: Zivanovic
authors.forename: Nikola
authors.initials: N
authors.lastname: Stefanovic
authors.forename: Srdjan
authors.initials: S
authors.lastname: Pesic
authors.forename: Dejana Ruzic
authors.initials: DR
authors.lastname: Zecevic
authors.forename: Jasmina R
authors.initials: JR
authors.lastname: Milovanovic
authors.forename: Slobodan M
authors.initials: SM
authors.lastname: Jankovic
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017298:Bisoprolol / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002908:Chronic Disease; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D017298:Bisoprolol