BIOAVAILABILITY OF PULMONARY DELIVERED PEPTIDES AND PROTEINS - ALPHA-INTERFERON, CALCITONINS AND PARATHYROID HORMONES

The intratracheal technique was used to study the pulmonary absorption of natural human alpha-interferon, parathyroid hormone (PTH) 1-84 and 1-34, salmon and human calcitonin, human glucagon and human somatostatin 1-28 in normal rats. Absolute pulmonary bioavailabilities were calculated from comparisons of area under the serum concentration curves (AUCs) following intravenous and intratracheal administrations. The presence of peptide in serum was measured by RIA or in the case of interferon with a specific bioassay. By the pulmonary route interferon had an absolute bioavailability > 56%; PTH 84, > 23%; PTH 34, approximate to 40%; salmon and human calcitonins, approximate to 17%; glucagon < 1%; and somatostatin < 1%. PTH 34 and the calcitonins peaked in the blood at about 15 min. Interferon had a more continuous and prolonged absorption which was not complete at 9 h. The rather striking permeability of the lung to peptide derivatives and proteins has important implications for the development of new human therapeutics.