BIOAVAILABILITY OF LEUPROLIDE FOLLOWING INTRATRACHEAL ADMINISTRATION TO BEAGLE DOGS

Leuprolide acetate is a nonapeptide with virtually no oral bioavailability. Studies were therefore conducted to evaluate pulmonary bioavailability of this drug when administered to the lung as an aerosol. Male and female beagle dogs were administered a solution aerosol formulation of leuprolide acetate at 0, 0.5, 1, and 2 mg/day for 14 consecutive days. Results from this study demonstrated: (1) significant plasma levels of leuprolide are obtained following administration of leuprolide to the lung compared to a placebo aerosol formulation as control; (2) plasma levels of circulating leuprolide indicate a linear dose-dependent increase in pulmonary bioavailability of leuprolide from the aerosol in the dose range of 0.5-2.0 mg/dog per day; (3) basic pharmacokinetic parameters estimated from the data show no significant differences in pulmonary absorption between male and female dogs; and (4) there is a corresponding decrease in plasma gonadotropins with sequential increase in plasma leuprolide concentrations. The results further indicate that an inhalation aerosol formulation of leuprolide could be a potential alternative to parenteral administration of this drug. These findings suggest that inhalation aerosol delivery may be effective for LHRH analogs and perhaps other peptides with oral absorption limitations. © 1990.