Abstract

A thermally generated aerosol (TGA) system can effect reliable delivery of excipient-free drug to alveoli, resulting in rapid systemic drug absorption. We developed a pharmacokinetic model of prochlorperazine, administered by inhalation and as a rapid intravenous infusion, and we determined absolute TGA bioavailability in eight healthy volunteers in this institutional review board-approved, two-period crossover study. After the drug was administered as either a 5-s intravenous infusion or a TGA single-breath inhalation, blood was collected at various times for up to 24 h. Plasma prochlorperazine concentrations were measured using liquid chromatography-tandem mass spectrometry. Inhalation and rapid intravenous administration produced similar plasma prochlorperazine concentration profiles. Intravenous and inhalation pharmacokinetics were well characterized by a simultaneous two-compartment model with multiple absorption delays. Prochlorperazine pharmacokinetic parameters were similar to those reported for single intravenous doses. The geometric mean bioavailability after TGA delivery was 1.10. The administration of prochlorperazine by inhalation resulted in pharmacokinetics similar to that seen after intravenous administration, in terms of speed, extent, and consistency of absorption.