umu.sePublications
Change search
ReferencesLink to record
Permanent link

Direct link
Potentiation of clopidogrel active metabolite formation by rifampicin leads to greater P2Y12 receptor blockade and inhibition of platelet aggregation after clopidogrel.
Show others and affiliations
2010 (English)In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 8, no 8Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:  The thienopyridine P2Y(12) receptor antagonist clopidogrel reduces the risk of arterial thrombosis and individual pharmacodynamic responses to clopidogrel are believed to reflect the levels of active metabolite (AM) generated. Rifampicin increases the inhibitory effect of clopidogrel on platelet aggregation (PA). We studied the response to clopidogrel before and during administration of rifampicin in order to study the relationship between individual AM levels and P2Y(12) blockade.

METHODS:  Healthy volunteers received a 600-mg loading dose of clopidogrel followed by 75 mg daily for 7 days and, after a washout period and treatment with rifampicin [300 mg twice a day (b.i.d.)], received the same regimen of clopidogrel. Clopidogrel AM levels were determined over 4 h after the clopidogrel loading dose and unblocked P2Y(12) receptor number was assessed using a (33) P-2MeSADP binding assay. PA was measured by optical aggregometry with ADP and TRAP.

RESULTS:  Rifampicin enhanced clopidogrel AM production [area-under-the-curve (AUC): clopidogrel 89±22 ng h mL(-1) , clopidogrel+rifampicin 335±86 ng h mL(-1) , P<0.0001], and P2Y(12) blockade (unblocked receptors: clopidogrel 48±24, clopidogrel+rifampicin 4±2, P<0.0001) and reduced PA (5 μmol L(-1) ADP: clopidogrel 20±4, clopidogrel+rifampicin 5±2, P<0.01). Increasing numbers of unblocked receptors were required for an aggregation response with a decreasing concentration of ADP. PA induced by ADP 2 μmol L(-1) was particularly sensitive to low levels of receptor blockade.

CONCLUSION:  Potentiation of clopidogrel AM production by rifampicin leads to greater P2Y(12) blockade and consequently greater inhibition of PA. PA responses to low concentrations of ADP are more sensitive to P2Y(12) blockade.

Place, publisher, year, edition, pages
2010. Vol. 8, no 8
Identifiers
URN: urn:nbn:se:umu:diva-110777DOI: 10.1111/j.1538-7836.2010.03925.xPubMedID: 20492465OAI: oai:DiVA.org:umu-110777DiVA: diva2:865459
Available from: 2015-10-28 Created: 2015-10-28 Last updated: 2015-10-28

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Buckland, R J
In the same journal
Journal of Thrombosis and Haemostasis

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 12 hits
ReferencesLink to record
Permanent link

Direct link