title: Population pharmacokinetics of carvedilol in patients with congestive heart failure.
abstract: The aim of this study was to derive population pharmacokinetic (PK) model for clearance (CL) of carvedilol in adult patients with chronic heart failure (CHF). Medication and demographic data were obtained from 52 Caucasian patients with CHF taking carvedilol. Population PK analysis was performed by nonlinear mixed-effects modeling (NONMEM) to estimate and identify different factors that could affect carvedilol CL. A total of 55 plasma concentrations were collected from 52 patients with mean age of 63.02 ± 11.95 years and total body weight (TBW) of 77.96 ± 13.46 kg. Total daily doses of carvedilol in the target population had wide range of variability (6.25-50 mg), followed by high variability of drug plasma concentrations (1-59.07 ng/mL). The typical mean value for carvedilol CL, estimated by the base model, in the target population was 43.8 L/h. The TBW, concomitant therapy with digoxin, and tobacco using were determinants of a derived population model. The final regression model for the CL of carvedilol is: [Formula: see text] Our results suggest that the TBW, concomitant therapy with digoxin, and tobacco using are the main subjects of carvedilol PK variability.
authors.affiliation: Pharmacology Department, Medical Faculty, University of Nis, Nis, Serbia.
authors.forename: Valentina N
authors.initials: VN
authors.lastname: Nikolic
authors.forename: Slobodan M
authors.initials: SM
authors.lastname: Jankovic
authors.forename: Radmila
authors.initials: R
authors.lastname: Velickovic-Radovanović
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: Tatjana
authors.initials: T
authors.lastname: Jevtovic-Stoimenov
authors.forename: Janko
authors.initials: J
authors.lastname: Djuric
authors.forename: Veroljub
authors.initials: V
authors.lastname: Markovic
authors.forename: Jasmina R
authors.initials: JR
authors.lastname: Milovanovic
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000097:blood*; D000368:Aged; D002227:Carbazoles / Q000097:blood*; D000077261:Carvedilol; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011412:Propanolamines / Q000097:blood*; D012044:Regression Analysis; D014665:Vasodilator Agents / Q000097:blood*
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol; D019389:Cytochrome P-450 CYP2D6
keywords: HPLC; clearance; cytohrome P450; genetic polymorphism; polymerase chain reaction; population pharmacokinetics