Linked Life Data

20686235

Source:http://linkedlifedata.com/resource/pubmed/id/20686235

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2010-8-5
pubmed:abstractText
Carvedilol is a beta-adrenoceptor antagonist used for treating chronic heart failure (CHF). Two clinical studies were conducted to evaluate the population pharmacokinetics and pharmacodynamics of R- and S-carvedilol, and associated covariates, in patients with CHF. Fifty-eight patients (male=45, female=13) with New York Heart Association class I-IV CHF were enrolled in two clinical studies. R- and S-carvedilol concentrations were measured using HPLC at steady-state after oral administration of carvedilol at 1.25-20 mg o.d. or b.i.d. The data from both studies were used to estimate the population pharmacokinetic parameters and covariates using the nonlinear mixed effects model program. For 40 patients evaluated in one clinical study, the cytochrome P450 (CYP)2D6 *1, *10, and *5 genotypes were determined using allele-specific primer PCR, and individual patients' oral clearance (CL/F) of both enantiomers were estimated by the empirical Bayes method. A one-compartment model with a first-order absorption rate was established, in which body weight and alpha(1)-acid glycoprotein were significant covariates. Individual CL/F values for carvedilol were significantly lower in Japanese CHF patients with the CYP2D6 *1/*5, *5/*10 and *10/*10 genotypes. Estimation of the population pharmacokinetic parameters and their covariates for each enantiomer in Japanese patients with CHF showed that the CL/F values for R- and S-carvedilol were dependent on body weight, alpha(1)-acid glycoprotein, and CYP2D6 genotype. Prediction of exposure to free plasma carvedilol is important for dosage adjustment of beta-blocker therapy in patients with CHF.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1347-5215
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1378-84
pubmed:meshHeading
pubmed-meshheading:20686235-Administration, Oral, pubmed-meshheading:20686235-Adrenergic beta-Antagonists, pubmed-meshheading:20686235-Adult, pubmed-meshheading:20686235-Aged, pubmed-meshheading:20686235-Aged, 80 and over, pubmed-meshheading:20686235-Bayes Theorem, pubmed-meshheading:20686235-Carbazoles, pubmed-meshheading:20686235-Chronic Disease, pubmed-meshheading:20686235-Cytochrome P-450 CYP2D6, pubmed-meshheading:20686235-Female, pubmed-meshheading:20686235-Gene Frequency, pubmed-meshheading:20686235-Genetics, Population, pubmed-meshheading:20686235-Genotype, pubmed-meshheading:20686235-Heart Failure, pubmed-meshheading:20686235-Humans, pubmed-meshheading:20686235-Japan, pubmed-meshheading:20686235-Male, pubmed-meshheading:20686235-Metabolic Clearance Rate, pubmed-meshheading:20686235-Middle Aged, pubmed-meshheading:20686235-Propanolamines, pubmed-meshheading:20686235-Stereoisomerism
pubmed:year
2010
pubmed:articleTitle
Population pharmacokinetics of R- and S-carvedilol in Japanese patients with chronic heart failure.
pubmed:affiliation
Department of Biopharmaceutics, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588, Japan.
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, Non-U.S. Gov't