Plasma concentrations and anti-platelet effects after low dose XXXX .

@entity2871 @entity117 @entity1281 @entity1423
The present study has investigated whether low-dose @entity117 ( @entity1281 ) can inhibit @entity1423 locally at its site of gastrointestinal absorption without concentrations in the systemic circulation high enough for inhibition of cyclooxygenase. For this purpose @entity1423 , @entity2871 formation as well as @entity1281 plasma concentrations were measured in 8 volunteers before oral intake of 100 mg @entity1281 as well as 20 to 300 minutes thereafter. At each time 5 ml of blood were mixed with 5 ml of blood obtained from a second, untreated volunteer. Aggregation and @entity2871 formation were also determined in these mixed blood samples. The same protocol was performed with 4 volunteers after administration of 1500 mg @entity1281 as well as after no drug intake. In a separate experiment the concentration-effect-relationship of @entity1281 was assessed in vitro. One hundred and forty minutes after administration of 100 mg @entity1281 aggregation and @entity2871 formation were significantly decreased to 49.4 and 4.5% of the initial values, respectively, whereas in the mixed blood sample aggregation was not impaired. Inhibition of @entity2871 formation was constantly 73% of the inhibition observed in the unmixed sample throughout the study period and thus most probably was caused by dilution of the platelets of the untreated volunteer by the inactivated platelets of the @entity1281 -treated volunteer. These data suggest the absence of pharmacologically active drug concentrations in the peripheral blood. @entity1281 plasma concentration was highest after 40 minutes (2.2 +/- 1.6 microgram/ml; n = 5). After the 1500 mg @entity1281 dose platelet function and @entity2871 formation decreased to 29.8 and 2.0% of the initial values, respectively. Furthermore, aggregation and @entity2871 formation in the mixed blood sample were markedly reduced. Thus, after the high dose of @entity1281 effective plasma concentrations were present in the peripheral circulation. Highest @entity1281 plasma concentrations were 21.1 +/- 8.9 micrograms/ml. IC50 values were 1.00 +/- 0.36 and 0.30 +/- 0.05 microgram/ml for aggregation and @entity2871 formation in vitro, respectively. It is concluded that low dose @entity1281 can effectively inhibit platelet function without producing pharmacologically active concentrations in the peripheral circulation.
