Experimental evidence of regional lung deposition differences effecting the systemic exposure in dog

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Summary

A pioneering experiment in dog was conducted using the PreciseInhale™ to investigate the technical delivery of regional lung deposition and its potential effect on systemic exposure. The aerosolisation equipment was used together with an apnoeic dog model for delivery of a low solubility drug substance to the lungs. Precise delivery to central and distal lung regions provided significantly different plasma exposures. The initial part of the plasma curve was experimentally determined to originate predominantly from the drug particles deposited in the more distal regions of the lungs. Hence, distal deposition of a drug substance was shown to have significantly faster absorption into the systemic circulation than if deposited in the more central region of the lungs. In silico modelling, conducted by the physiologically based biopharmaceutical prediction tool Lung-SIM; in vitro real time monitoring of aerosol particles; and in vivo generated plasma exposure data, all supports the conclusion of successful regional lung deposition in the dogs by the PreciseInhale™ equipment. This novel investigation provides the previously stated hypotheses with experimental evidence of the postulated differences in the absorption rates from the central and distal regions within the lungs.