RT Journal Article
SR Electronic
T1 Recirculatory Pharmacokinetic Model of the Uptake, Distribution, and Bioavailability of Prochlorperazine Administered as a Thermally Generated Aerosol in a Single Breath to Dogs
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 262
OP 267
DO 10.1124/dmd.106.010652
VO 35
IS 2
A1 Michael J. Avram
A1 Thomas K. Henthorn
A1 Daniel A. Spyker
A1 Tom C. Krejcie
A1 Peter M. Lloyd
A1 James V. Cassella
A1 Joshua D. Rabinowitz
YR 2007
UL http://dmd.aspetjournals.org/content/35/2/262.abstract
AB A thermal aerosol generation process is capable of delivering pure drug reliably to the alveoli where it is absorbed systemically. Although deep lung absorption of drugs administered as an aerosol has been shown to be rapid, detailed characterization of their absorption and distribution has not been reported. The present study describes the pharmacokinetics of prochlorperazine from the moment of administration as either a rapid intravenous infusion or a thermally generated aerosol and determines the bioavailability of the aerosol by two independent methods. Prochlorperazine disposition was determined in four anesthetized dogs after a 5-s intravenous infusion and after thermally generated aerosol administration in one breath. Venous blood samples were collected frequently from the time of drug administration to 24 h and left ventricular blood samples were drawn more often until 10 min after drug administration. Prochlorperazine disposition after intravenous and aerosol administration was characterized by fitting a recirculatory model to left ventricular and venous drug concentration data simultaneously. Prochlorperazine aerosol administration produced plasma drug concentrations similar to those after rapid intravenous administration of the same nominal dose, with peak left ventricular concentrations achieved in less than 30 s. Plasma concentration profiles of prochlorperazine administered by both routes were well described by the recirculatory model. Bioavailability of the thermally generated aerosol was consistent and averaged more than 80% of emitted dose. Pulmonary administration of a thermally generated drug aerosol in one breath may be a viable alternative to rapid intravenous administration of drugs requiring rapid and predictable production of effective plasma concentrations. The American Society for Pharmacology and Experimental Therapeutics