Search: onr:"swepub:oai:DiVA.org:uu-105102" >
Genetic variation o...
Genetic variation of CYP2C19 affects both pharmacokinetic and pharmacodynamic responses to clopidogrel but not prasugrel in aspirin-treated patients with coronary artery disease
-
- Varenhorst, Christoph, 1977- (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,UCR
-
- James, Stefan, 1964- (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,UCR
-
- Erlinge, David (author)
- Lund University,Lunds universitet,Kardiologi,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Cardiology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine
-
show more...
-
Brandt, John T. (author)
-
- Braun, Oscar (author)
- Lund University,Lunds universitet,Kardiologi,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Cardiology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine
-
Man, Michael (author)
-
- Siegbahn, Agneta, 1947- (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper
-
Walker, Joseph (author)
-
- Wallentin, Lars, 1943- (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,UCR
-
Winters, Kenneth J. (author)
-
Close, Sandra L. (author)
-
show less...
-
(creator_code:org_t)
- 2009-05-09
- 2009
- English.
-
In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 30:14, s. 1744-1752
- Related links:
-
https://academic.oup...
-
show more...
-
http://dx.doi.org/10...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
https://lup.lub.lu.s...
-
show less...
Abstract
Subject headings
Close
- Aims The metabolic pathways leading to the formation of prasugrel and clopidogrel active metabolites differ. We hypothesized that decreased CYP2C19 activity affects the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. Methods and results Ninety-eight patients with coronary artery disease (CAD) taking either clopidogrel 600 mg loading dose (LD)/75 mg maintenance dose (MD) or prasugrel 60 mg LD/10 mg MD were genotyped for variation in six CYP genes. Based on CYP genotype, patients were segregated into two groups: normal function (extensive) metabolizers (EM) and reduced function metabolizers (RM). Plasma active metabolite concentrations were measured at 30 min, 1, 2, 4, and 6 h post-LD and during the MD period on Day 2, Day 14, and Day 29 at 30 min, 1, 2, and 4 h. Vasodilator-stimulated phosphoprotein (VASP) and VerifyNow P2Y12 were measured predose, 2, and 24 +/- 4 h post-LD and predose during the MD period on Day 14 +/- 3 and Day 29 +/- 3. For clopidogrel, active metabolite exposure was significantly lower (P = 0.0015) and VASP platelet reactivity index (PRI, %) and VerifyNow P2Y(12) reaction unit (PRU) values were significantly higher (P < 0.05) in the CYP2C19 RM compared with the EM group. For prasugrel, there was no statistically significant difference in active metabolite exposure or pharmacodynamic response between CYP2C19 EM and RM. Variation in the other five genes demonstrated no statistically significant differences in pharmacokinetic or pharmacodynamic responses. Conclusion Variation in the gene encoding CYP2C19 in patients with stable CAD contributes to reduced exposure to clopidogrel's active metabolite and a corresponding reduction in P2Y(12) inhibition, but has no significant influence on the response to prasugrel.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Keyword
- Clopidogrel
- Prasugrel
- Cytochrome P450 enzymes
- CYP2C19
- Pharmacogenetics
- MEDICINE
- MEDICIN
- Cytochrome P450 enzymes
- Clopidogrel
- Prasugrel
- CYP2C19
- Pharmacogenetics
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Varenhorst, Chri ...
-
James, Stefan, 1 ...
-
Erlinge, David
-
Brandt, John T.
-
Braun, Oscar
-
Man, Michael
-
show more...
-
Siegbahn, Agneta ...
-
Walker, Joseph
-
Wallentin, Lars, ...
-
Winters, Kenneth ...
-
Close, Sandra L.
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Clinical Medicin ...
-
and Cardiac and Card ...
- Articles in the publication
-
European Heart J ...
- By the university
-
Uppsala University
-
Lund University