Effects of dazoxiben and low‐dose aspirin on platelet behaviour in man.

Abstract

1 We have studied the effects on platelet behaviour of ingestion of the thromboxane synthetase inhibitor dazoxiben (UK 37248), by healthy subjects, and compared the results with the effects of a low dose of aspirin (a cyclo-oxygenase inhibitor), and of a combination of dazoxiben and a low dose of aspirin. 2 Dazoxiben ingestion prevented the release reaction induced by sodium arachidonate (NaAA) in platelet-rich plasma (PRP) from some individuals ("responders") but not in PRP from others ("non-responders"). In vitro testing of PRP from the same subjects, incubated with 10-4M dazoxiben, correlated with the effect of dazoxiben ingestion on NaAA-induced release. Platelets from "non-responders" tended to undergo a more extensive release reaction than platelets from "responders" even in the absence of any drug although there was some overlap between the results in the two groups. Platelets from "non-responders" required significantly lower concentrations of NaAA to induce release reaction than platelets from "responders". Platelets from "responders" and "non-responders" did not differ in the amount of malondialdehyde (MDA) produced or in the effectiveness with which dazoxiben ingestion inhibited MDA production. 3 Low dose aspirin had comparable effects on NaAA-induced release to dazoxiben, but in contrast to dazoxiben, the effectiveness of low-dose aspirin in inhibiting NaAA induced release reaction was related to its effectiveness in inhibiting MDA generation. 4 Neither dazoxiben nor low-dose aspirin significantly affected the release reaction induced by adenosine diphosphate (ADP), although both drugs significantly inhibited adrenaline-induced release. 5A combination of dazoxiben and low dose aspirin had a greater effect on platelet behaviour in response to NaAA, ADP, and adrenaline than either drug alone.

Human blood platelet behaviour after inhibition of thromboxane synthetase.

“…The amounts of TXA2 that were used are expressed in terms of MDA equivalents. becomes more extensive as the concentration of the agonist is increased whereas the NaAA-induced release reaction does not (Jones et al, 1982). In addition, the release reaction induced by TXA2 is less extensive than that induced by NaAA (Figure 4).…”

“…We referred to individuals for whom 10-4M UK 34787 inhibited aggregation and release as "responders" and those for whom 10-4M UK 34787 did not inhibit aggregation and did not prevent release as "nonresponders". Studies that we and others have carried (©The Macmillan Press Ltd 1983 out using other inhibitors of thromboxane synthetase -dazoxiben (Bertele et al, 1981, Vermylen et al, 1981, Jones et al, 1982 and 7-(imidazolyl)heptanoic acid (Grimm et al, 1981;Butler et al, 1982) We have also studied platelet reactivity in patients with maturity-onset diabetes and in age-and sexmatched controls. In PRP from eight of the controls 10-4M UK-34787 inhibited NaAA-induced platelet behaviour whereas in 12 it did not.…”

Management of type-2 diabetes with anti-platelet therapies special reference to aspirin

“…Aspirin (acetyl salicylic acid) is the most costeffective anti-platelet drug available for primary and secondary prophylaxis of acute coronary syndromes. Aspirin at a dose of 80-160 mgs has been shown to offer significant benefit in alleviating platelet-related clinical complications in a variety of thrombotic situations (74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89)(90)(91)(92)(93). Single oral doses of 10-100 mgs of aspirin can significantly inhibit the platelet PG synthase activity (74).…”

Effects of the selective inhibition of platelet thromboxane synthesis on the platelet‐subendothelium interaction

“…Pharmacological studies have used inhibitors of TxA 2 synthesis to diminish platelet activation as one way to prevent arterial thrombosis (Jones et al ., 1983; Tayler et al ., 1981). Cyclo‐oxygenase inhibitors decrease TxA 2 and prostacyclin synthesis.…”