Compared effects of the two antiinflammatory drugs indoprofen and lonazolac on thromboxane generation and on platelet aggregation, related to plasma concentrations after single oral doses.
Single doses of indoprofen 100 mg and lonazolac-Ca 200 mg were given orally to eight healthy volunteers. Blood samples were taken prior to and at various times until 24 hours after the dose. Drug concentrations in plasma were analyzed by HPLC and thromboxane B2 (TXB2) in serum by radioimmunoassay. Platelet aggregation in plasma was induced by various concentrations of arachidonic acid and evaluated with respect to different phases in the aggregatory response. The drugs were rapidly absorbed and for both compounds the decline in plasma concentrations described two phases. Although concentrations of indoprofen were up to ten times higher than those of lonazolac, the two drugs were almost equally potent inhibitors of generation of TXB2, with IC50 for indoprofen of 1.4-1.5 X 10(-7) M and for lonazolac 2.1-3.0 X 10(-7) M. Their effects on the lag phase in platelet aggregation paralleled the inhibition of TXB2 formation. However, the rate and extent of aggregation were more inhibited by indoprofen than by lonazolac, and the discrepancy was greater than would be expected from concomitant values for TXB2 suppression. The rate of aggregation appeared to be the most sensitive variable, since the extent of aggregation followed an all-or-none pattern. The present results show that the concentrations reached after clinically used doses of antiinflammatory drugs may vary widely in relation to the concentrations needed for maximum inhibition of platelet cyclooxygenase. The results from aggregation tests may support the idea that non-steroid antiinflammatory drugs can differ in their mechanisms of action.
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007216:Indoprofen / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D008297:Male; D010666:Phenylpropionates / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D011720:Pyrazoles / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000096:biosynthesis*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010666:Phenylpropionates; D011720:Pyrazoles; C017472:lonazolac; D013929:Thromboxane B2; D007216:Indoprofen