Effects of 1-S replaced and/or decarboxylated latamoxef on rabbit platelet aggregation in vitro

Latamoxef, 1-S replaced and/or decarboxylated derivatives of latamoxef were examined for their effects on ADP-, collagen- and platelet activating factor (PAF)-induced rabbit platelet aggregation in vitro. The results were compared with those of cefotaxime, cefmetazole, carbenicillin and aspirin. Latamoxef produced a dose-dependent inhibition of platelet aggregation at concentrations over about 4 mM, and the potency was almost similar to that produced by the other beta-lactam antibiotics, although the inhibiting effect of ADP-induced aggregation was more potent for latamoxef, whereas that on collagen-induced aggregation was stronger for cefmetazole and carbenicillin. The inhibitory effect of beta-lactam antibiotics on collagen-induced aggregation was, however, much weaker than that of aspirin. With respect to drug potency, replacement of the oxygen atom in the oxacephem ring with a sulfur atom caused no significant change in ADP-induced aggregation or slightly stronger inhibition of collagen- and PAF-induced aggregations. The decarboxylated derivatives of latamoxef and the 1-S replaced analogue of latamoxef showed slightly weaker inhibition of ADP-induced aggregation, but much stronger inhibition of collagen- and PAF-induced aggregation than the parent compounds. These data suggest that 1) the oxygen atom in the oxacephem ring is not responsible for the inhibitory effect of latamoxef on platelet aggregation and 2) the carboxyl group in the amide side chain had no significant role in this inhibition.