Drug/drug interaction of common NSAIDs with antiplatelet effect of aspirin in human platelets
IR@CDRI: CSIR-Central Drug Research Institute, Lucknow
View Archive Info| Field | Value | |
| Creator |
Saxena, Aaruni
Balaramnavar, V M Hohlfeld, Thomas Saxena, A K |
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| Date |
2014-06-13T11:44:55Z
2014-06-13T11:44:55Z 2013 |
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| Identifier |
European Journal of Pharmacology, 2013, 721, 215-224
http://hdl.handle.net/123456789/1273 |
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| Description |
Nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with the anti-platelet activity of aspirin at the level of the platelet cyclooxygenase-1 (COX-1) enzyme. In order to examine the interference of common NSAIDs with the anti-platelet activity of aspirin the human platelet rich plasma from voluntary donors was used for arachidonic acid-induced aggreation and determination of thromboxane synthesis. Further, docking studies were used to explain the molecular basis of the NSAID/aspirin interaction. The experimental results showed that celecoxib, dipyrone (active metabolite), ibuprofen, flufenamic acid, naproxen, nimesulide, oxaprozin, and piroxicam significantly interfere with the anti-platelet activity of aspirin, while diclofenac, ketorolac and acetaminophen do not. Docking studies suggested that NSAIDs forming hydrogen bonds with Ser530, Arg120, Tyr385 and other amino acids of the COX-1 hydrophobic channel interfere with antiplatelet activity of aspirin while non interfering NSAIDs do not form relevant hydrogen bond interactions within the aspirin binding site. In conclusion, docking analysis of NSAID interactions at the COX-1 active site appears useful to predict their interference with the anti-platelet activity of aspirin. The results, demonstrate that some NSAIDs do not interfere with the antiplatelet action of aspirin while many others do and provide a basis for understanding the observed differences among individual non-aspirin NSAIDs.
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575944 bytes
application/pdf |
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| Language |
en
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| Relation |
CSIR-CDRI communication no. 8543
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| Subject |
Aspirin
Drug/Drug Interaction Molecular Modeling Aggregation Thromboxane |
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| Title |
Drug/drug interaction of common NSAIDs with antiplatelet effect of aspirin in human platelets
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| Type |
Article
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