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Author: Admin | 2025-04-28
Response to aspirin was related to the haplotype (the pattern of variants in an individual), without a clear explanation, as only one variant was predicted to affect the structure of the protein. Whether other variants (possibly linked to the known variants) exist has yet to be addressed, requiring resequencing of the gene in a larger population.26 Others associated aspirin resistance, determined by the PFA-100 point-of-care platelet function assay (collagen and epinephrine cartridge) with increased expression of three vitamin D–binding protein isotypes.27 In effect, genetic variation in any platelet-signaling component, whether directly targeted by a drug or not, has the potential to influence drug response. This is borne out by a recent study of healthy volunteers showing that both baseline platelet function and persistent platelet activation in the presence of aspirin largely reflected signaling via COX-1–independent pathways and that this was an inherited trait.25 Not surprisingly, platelet activity and bleeding time response to antiplatelet therapy are to some extent inherited.2,28 Aspirin and Nonsteroidal Antiinflammatory Drugs There is one circumstance in which the pharmacologic response to aspirin may be impaired, namely when a nonsteroidal anti-inflammatory drug (NSAID) has been administered prior to aspirin. This has been reported primarily with ibuprofen, a nonselective cyclooxygenase inhibitor. Ibuprofen inhibits COX-1 in part through binding to the arginine-120 at the mouth to the substrate-binding site. The drug has a long plasma half-life (4–6 hours) and therefore inhibits the enzyme for several hours. In so doing, ibuprofen prevents aspirin from accessing the target serine in the active site. As aspirin is rapidly inactivated to form salicylate, and therefore is active for a relatively short period, it fails to inactivate the enzyme. Ibuprofen is a reversible inhibitor of COX-1 and washes out, leaving the enzyme uninhibited. In effect, prior dosing with ibuprofen blocks the inhibition by aspirin.29 There
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