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Title: Population pharmacokinetics of carvedilol in patients with congestive heart failure
Authors: Nikolic V.
Jankovic, Slobodan
Veličković-Radovanović R.
Apostolovic, Svetlana
Stanojevic D.
Živanović, Slavoljub
Stefanović, Nikola
Pesic, Srdjan
Jevtovic Stoimenov, Tatjana
Djuric, Janko
Grbovic-Markovic V.
Milovanovic, Jasmina
Journal: Journal of Pharmaceutical Sciences
Issue Date: 1-Jan-2013
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: CL(L/h) = 10 + 0.434 TBW + 22.5 Digoxin + 29.9 Tobacco Our results suggest that the TBW, concomitant therapy with digoxin, and tobacco using are the main subjects of carvedilol PK variability. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.
Type: Article
DOI: 10.1002/jps.23626
ISSN: 00223549
SCOPUS: 84881029832
Appears in Collections:Faculty of Medical Sciences, Kragujevac
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