THE INFLUENCE OF REGIONAL DEPOSITION ON THE PHARMACOKINETICS OF PULMONARY-DELIVERED HUMAN GROWTH-HORMONE IN RABBITS

The pulmonary deposition and pharmacokinetics of human growth hormone (hGH), administered by aerosol and instillate, in formulations contain ing Tc-99m-DTPA (for gamma scintigraphic imaging) have been studied in five male New Zealand White rabbits. Gamma scintigraphy indicated tha t the peripheral:central deposition tended to be greater for aerosol ( 1.54) than for instillate (0.8). Two gamma scintigraphic methods were used to quantify dose deposited by aerosol, which permitted bioavailab ilities to be determined. The bioavailable fraction for aerosolized hG H (45%) was greater than for instilled hGH (16%). This was attributed to the differential effects of mucociliary clearance. Absorption rate limited pharmacokinetics prevailed for both hGH formulations with post -peak half-lives approximately 10-fold greater than the intravenous el imination half-life of 40 min. Apparent absorption rate constants resu lting from instillation and aerosolization were equivalent (0.0012 min (-1) and 0.0020 min(-1) respectively), however lung-to-blood transfer rate constants for aerosol delivery (0.00071 min(-1)) were greater tha n for instillation (0.00018 min(-1)).