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  • Title: Pharmacologic properties of FPL 55712 administered by aerosol.
    Author: O'Donnell M, Welton AF.
    Journal: Agents Actions; 1984 Jan; 14(1):43-8. PubMed ID: 6322547.
    Abstract:
    FPL 55712 was investigated by the aerosol route of administration for efficacy at protecting against leukotriene-induced bronchoconstrictions in guinea pigs and for mediator release inhibitory activity in passively sensitized rats. In the studies to investigate leukotriene antagonism; anesthetized, spontaneously breathing guinea pigs were pretreated with propranolol and were exposed via tracheal cannula to aerosols generated by a Monaghan nebulizer. Subsequently, the animals were artificially ventilated and challenged with LTD4 or LTE4 (25 micrograms/kg, i.v.). FPL 55712 produced a concentration-dependent inhibition of LTD4 and LTE4-induced bronchoconstriction (IC50's 0.5% and 0.8%, respectively). Although the biologic half-life of FPL 55712, administered intravenously, was very short (1.7 minutes against LTD4 and 1.2 minutes against LTE4) after aerosol administration the biological half-life was surprisingly long (120 minutes against LTD4 and 90 minutes against LTE4). Aerosolized FPL 55712 also possessed weak antiallergic activity in comparison to disodium cromoglycate when measured as an inhibitor of IgE-mediated anaphylactic bronchoconstriction in rats (IC50's of 2.0% and 0.01%, respectively). Thus, these studies demonstrate that, when administered by aerosol, FPL 55712 is effective at protecting against leukotriene-induced bronchoconstrictions, exhibits a long duration of action and also possesses weak antiallergic activity.
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