アスピリンの抗血小板作用に及ぼす非ステロイド性抗炎症薬の影響に関する研究:-ヒト血液添加実験系を用いた検討-
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Low dose aspirin acts as an antiplatelet agent through irreversible acetylation of platelet cyclooxygenase (COX)-1,which inhibits platelet aggregation.Nonsteroidal anti-inflammatory drugs (NSAIDs) have a similar mechanism of action to aspirin,and may interact pharmacodynamically with it.In view of this,we performed an in vitro experimental study in which 6 NSAIDs with various COX-1 activities were added to human blank blood to investigate the influence of each one on the antiplatelet action of aspirin.Platelet rich plasma (PRP) was obtained from 8 healthy volunteers (23.3±3.2 years old).After adding aspirin (plasma concn.: 16μg/mL) and NSAIDs (plasma concn.: maximal concentration in clinical use) to the PRP,aggregation was measured using collagen as the stimulus.We used the platelet-aggregation threshold index (PATI) as the index of aggregation activity for this study.The PATI of a group in which aspirin was added after ibuprofen (Ibu→Asp) and that of a group in which both drugs were added at the same time (Asp+Ibu) were 3.54±0.80 and 3.53±1.01μg/mL,respectively.These were lower than the PATI for aspirin alone (5.17±1.18μg/mL),indicating interference with the antiplatelet effect by the NSAID.For the other 5 NSAIDs,the PATI obtained was similar to that for aspirin,regardless of the order of addition.The logarithmic value of the unbound drug concentration of each NSAID (Df) divided by platelet COX-1 IC50[log (Df/COX-1 IC50)]was correlated with its PATI (R=0.817,p<0.001),suggesting that the interaction between low dose aspirin and NSAIDs may be inferred from the level of inhibition of platelet COX-1 at clinical drug concentrations.
- 日本医療薬学会の論文
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