Abstract
Low-dose aspirin,an antiplatelet agent,acts by irreversibly acetylating internal cyclooxygenase-1 (COX-citation=1)on platelets,and is effective in the secondary prevention of cardiovascular events.However,as loxoprofen sodium also inhibits COX-1reversibly,its coadministration with aspirin may suppress the latter’s antiplatelet effect.We performed single- and multipledaily-dose studies in healthy volunteers to investigate the antiplatelet effect of aspirin when given with loxoprofen sodiumand determined a method for avoiding any interaction between the 2 drugs.We administered aspirin and loxoprofen sodium in the following manner in the single-daily-dose study : aspirin and loxoprofensodium administered at the same time or with a two-hour interval between them.In the multiple-daily-dose study,drugs were taken for four days as follows : aspirin (after breakfast),loxoprofen sodium (after every meal),both drugs givenat the same time in the morning,and taking aspirin before loxoprofen sodium in the morning.We measured platelet aggregationand serum thromboxane B2,and calculated the platelet aggregation threshold index (PATI) as the index of aggregationactivity,which was defined as the putative stimulus-concentration giving 50% aggregation.In the multiple-daily-dose study,when both drugs were taken at the same time,the PATI was 2.20±0.43μg/mL,suggestingthat the antiplatelet effect of aspirin had been decreased due to weak platelet COX-1 inhibition.On the other hand,when aspirin was taken before loxoprofen sodium the PATI was 5.29±0.59μg/mL,similar to that for aspirin only (5.51±0.59μg/mL).Therefore,though the antiplatelet effect of aspirin was suppressed by loxoprofen sodium,this interactioncould be avoided by taking aspirin 2 hours before loxoprofen sodium in the morning.
