The Pharmacokinetics and Bioavailability of Prochlorperazine Delivered as a Thermally Generated Aerosol in a Single Breath to Volunteers

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...

Full description

Saved in:
Bibliographic Details
Published in:Clinical pharmacology and therapeutics 2009-01, Vol.85 (1), p.71-77
Main Authors: Avram, MJ, Spyker, DA, Henthorn, TK, Cassella, JV
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aerosols
Area Under Curve
Biological and medical sciences
Biological Availability
Cross-Over Studies
Female
Humans
Infusions, Intravenous
Male
Medical sciences
Middle Aged
Models, Biological
Pharmacology. Drug treatments
Prochlorperazine - administration & dosage
Prochlorperazine - blood
Prochlorperazine - pharmacokinetics
Young Adult
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Clinical Pharmacology & Therapeutics (2008); 85, 1, 71–77 doi:10.1038/clpt.2008.184
ISSN:0009-9236
1532-6535
DOI:10.1038/clpt.2008.184