Protective activity of ketoprofen lysine salt against the pulmonary effects induced by bradykinin in guinea-pigs.

We investigated the capacity of ketoprofen lysine salt (KLS) to counteract the pulmonary effects of some mediators of airway inflammation. The protective effect of KLS and its R-isomer against bradykinin (BK) induced plasma extravasation in the airways and bronchoconstriction was evaluated in anaesthetized guinea-pigs, in parallel with the capacity of KLS to inhibit the production of thromboxane A2 (TXA2). Moreover, we studied the ability of KLS to modulate leukotriene C4 (LTC4) and acetylcholine (ACH) induced bronchoconstriction and the associated production of TXA2. Nimesulide (NIM) was used as the reference compound. KLS dose-dependently inhibited the bronchoconstriction and the associated production of TXA2 induced by BK, with closely related ID50 values of 31.2 and 34.0 micrograms/kg i.v., respectively. The protection was evident 10 min after KLS administration and, at 100 micrograms/kg i.v., lasted up to 2h, Moreover, KLS dose-dependently inhibited the increase in capillary permeability induced by BK, with a potency (ID50 23.4 micrograms/kg i.v.) slightly higher than that shown against the bronchoconstriction. KLS also prevented the bronchoconstriction and TXA2 production triggered by LTC4, but not ACH induced bronchoconstriction. In all the models studied, KLS was about 10 times more potent than NIM. These data demonstrate the capacity of KLS to counteract the bronchoconstriction induced by BK and LTC4 and to a large extent the airway inflammation induced by BK. Blockade of prostanoid production is likely to account for this protective effect, since the R-isomer of KLS was devoid of significant activity.