Search: WFRF:(Hjalmarson Åke 1937)
> (2010-2014) >
An Investigation of...
An Investigation of CYP2D6 Genotype and Response to Metoprolol CR/XL During Dose Titration in Patients With Heart Failure: A MERIT-HF Substudy
-
Batty, J. A. (author)
-
Hall, A. S. (author)
-
White, H. L. (author)
-
show more...
-
- Wikstrand, John, 1938 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
-
de Boer, R. A. (author)
-
van Veldhuisen, D. J. (author)
-
van der Harst, P. (author)
-
- Waagstein, Finn, 1938 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
-
- Hjalmarson, Åke, 1937 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
-
Kjekshus, J. (author)
-
Balmforth, A. J. (author)
-
show less...
-
(creator_code:org_t)
- 2013-09-30
- 2014
- English.
-
In: Clinical Pharmacology & Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 95:3, s. 321-330
- Related links:
-
https://gup.ub.gu.se...
-
show more...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- To explore the pharmacogenetic effects of the cytochrome P450 (CYP) 2D6 genotype in patients with systolic heart failure treated using controlled/extended-release (CR/XL) metoprolol, this study assessed the CYP2D6 locus for the nonfunctional * 4 allele (1846G> A; rs3892097) in the Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF; n = 605). Participants were characterized as extensive, intermediate, or poor metabolizers (EMs, IMs, or PMs, respectively), based on the presence of the CYP2D6* 4 allele (EM: * 1* 1, 60.4%; IM: * 1* 4, 35.8%; and PM: * 4* 4, 3.8%). Plasma metoprolol concentrations were 2.1-/4.6-fold greater in the IM/PM groups as compared with the EM group (P < 0.0001). Metoprolol induced significantly lower heart rates and diastolic blood pressures during early titration, indicating a CYP2D6* 4 allele dose-response effect (P < 0.05). These effects were not observed at maximal dose, suggesting a saturable effect. Genotype did not adversely affect surrogate treatment efficacy. CYP2D6 genotype modulates metoprolol pharmacokinetics/pharmacodynamics during early titration; however, the MERIT-HF-defined titration schedule remains recommended for all patients, regardless of genotype.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Keyword
- RANDOMIZED INTERVENTION TRIAL
- CYTOCHROME-P450 2D6
- ANKYLOSING-SPONDYLITIS
- CLINICAL-OUTCOMES
- ADVERSE EVENTS
- BETA-BLOCKERS
- TASK-FORCE
- PHARMACOKINETICS
- METABOLISM
- OXIDATION
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Batty, J. A.
-
Hall, A. S.
-
White, H. L.
-
Wikstrand, John, ...
-
de Boer, R. A.
-
van Veldhuisen, ...
-
show more...
-
van der Harst, P ...
-
Waagstein, Finn, ...
-
Hjalmarson, Åke, ...
-
Kjekshus, J.
-
Balmforth, A. J.
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Basic Medicine
-
and Pharmacology and ...
- Articles in the publication
-
Clinical Pharmac ...
- By the university
-
University of Gothenburg