Background: Pituitary adenylate cyclase activating polypeptide 1-38 (PACAP38) displays biological activities (e.g. bronchodilatory, pulmonary vasodilatory and anti-inflammatory properties) that are relevant in several pulmonary diseases. The aim of this study was to assess the safety and tolerability and the pulmonary and systemic effects of inhaled PACAP38 in humans.
Materials and methods: Twelve healthy male subjects (mean age 28) were studied in a randomized, double-blind, placebo-controlled dose escalation trial with inhalation of PACAP38 to a cumulative dose of 480 microg. Lung function was measured by body plethysmography. Systemic absorption was evaluated by plasma levels, skin blood flux (estimated by laser Doppler imager fluxmetry) and systemic haemodynamics.
Results: Inhalation of PACAP38 did not cause relevant adverse reactions or an increase of PACAP38 plasma levels. No statistically significant changes in lung function tests and no systemic effects (blood pressure, pulse rate or skin blood flux) occurred.
Conclusion: Inhaled PACAP38 was well tolerated without systemic side-effects in healthy male subjects.