The potential interactions between low-dose aspirin and naproxen co-administered to four healthy subjects on platelet TX biosynthesis in vivo and ex vivo and platelet aggregation induced by AA (1 mmol/l) ex vivo (25) were evaluated in two different studies (Figure 1). In the first study, uncoated aspirin (100 mg daily, at 8 am) to be swallowed whole was given for 6 consecutive days, and then the combination of aspirin and naproxen was administered for further 6 days: aspirin was given 2 h before naproxen (500 mg BID, at 10 am and 10 pm). After a washout period of 14 days, the treatments were administered in reverse order, i.e., low-dose aspirin (100 mg daily at 10 am) was taken 2 h after naproxen (500 mg BID, at 8 am and 8 pm) for further 6 days. Blood samples were collected before and at 2, 5, 14, and 26 h after the first study drug on the 6th, 12th, 27th, and 32nd study day to assess the inhibition of serum TXB2 (a capacity index of platelet COX-1 activity) (24) and lipopolysaccharide-induced prostaglandin (PG)E2 production (a capacity index of monocyte COX-2 activity) (26). Three consecutive urinary samples (time of collection: 0 to 6 h, 6 to 12 h, and 12 to 24 h were collected before treatment and on days 6, 12, 27, and 32 to evaluate the urinary excretion of 11-dehydro-TXB2 (a major enzymatic metabolite of TXB2 that is an index of TXA2 biosynthesis in vivo) (27). In the second study, a single dose of aspirin (100 mg) and naproxen (500 mg) was administered concurrently to 5 healthy subjects, and peripheral blood samples were collected before and up to 14 days after dosing to assess the time-dependent inhibition and recovery of serum TXB2 production and platelet aggregation ex vivo. Platelet aggregation induced by AA (1 mmol/l) was measured in platelet-rich plasma (25) using a Chrono-Log platelet aggregometer (Chrono-log Corp., Havertown, Pennsylvania), whereas immunoreactive TXB2, PGE2, and 11-dehydro-TXB2 were measured by previously validated radioimmunoassay techniques (24,26- 27).