The aim of this study was to construct a reliable dry powder inhalation (DPI) testing system for use in guinea pigs. Using this system, we were able to demonstrate the superiority of pulmonary administration of hydrophilically surface-modified pranlukast hydrate powder (SM-DP) over IV and PO administration as reflected in improved pharmacological action. Our ultimate aim is the development of an ideal treatment system for bronchial asthma involving topical administration to the lung.Methods
The reliability of the present DPI system was validated by continuously monitoring the concentration and particle size distribution of aerosols generated with an ambient particulate monitor and an Andersen air sampler, respectively. The pharmacological effect of SM-DP intratracheally administered to guinea pig was investigated by measuring the degree of bronchoconstriction and microvascular leakage induced by leukotriene D4.Results
The mass concentration of aerosols generated by the DPI system was stable and the mass median aerodynamic diameter of aerosols insufflated from the respirator of the DPI system ranged from 1.4 to 1.7 μm, within respirable limits. Inhibition of bronchoconstriction and airway microvascular leakage induced by leukotriene D4 was achieved successfully with a dramatically lower dose of DP, or a further lower dose of SM-DP, comparable with that of the drug solution injected intravenously. The plasma pranlukast hydrate level with SM-DP at 50% inhibition of bronchoconstriction and airway microvascular leakage was reduced to 1/10 or less that following IV and PO administration.Conclusions
The hydrophilically surface-modified pranlukast hydrate powders were ideally aerosolized by the present DPI system, and were uniformly deposited in the lung lobes after inhalation. The pulmonary administration system with SM-DP is strongly recommended as an ideal system for the treatment of bronchial asthma in order to avoid systemic side-effects due to a dramatically reduced ED50, comparable with or lower than IV, and the low plasma concentration of drug, 1/12 or less than that following IV and PO administration.