title: Multiple dose pharmacokinetics of inhaled loxapine in subjects on chronic, stable antipsychotic regimens.
abstract: This randomized, double-blind, placebo-controlled, parallel-group study was to determine the pharmacokinetic characteristics, safety, and tolerability of multiple doses of inhaled loxapine aerosol in subjects on a stable, oral, chronic antipsychotic regimen. Loxapine was delivered by means of a unique thermally generated aerosol comprising drug particles of a size designed for deep lung delivery and absorption. Thirty-two subjects were randomized 1:1:1:1 to receive inhaled loxapine (total doses of 15, 20, or 30 mg) or inhaled placebo administered in 3 divided doses, given 4 hours apart. Following inhalation, the median Tmax was 2 minutes, and concentrations declined to about half Cmax approximately 5 minutes later across the 3 dose levels. The dose proportionality across data from this study combined with data from the single-dose study showed a slope (90%CI) of log AUCinf versus log dose of 0.818 (0.762-0.875) across the 8 doses (n = 60 subjects) studied, indicating reasonable dose proportionality. The most common adverse events were cough (3 of 32, 9%), sedation (3 of 32, 9%), and dysgeusia (2 of 32, 6%). The inhalation of multiple doses of inhaled loxapine were well tolerated in study subjects and provided a safe, well-tolerated means for rapidly and reliably achieving therapeutic plasma concentrations of loxapine. ClinicalTrials.gov identifier: NCT00555412.
authors: Alexza Pharmaceuticals, Inc., Mountain View, CA, USA.
authors: Daniel A
authors: DA
authors: Spyker
authors: Atlanta Center for Medical Research, Atlanta, GA, USA.
authors: Robert A
authors: RA
authors: Riesenberg
authors: Alexza Pharmaceuticals, Inc., Mountain View, CA, USA.
authors: James V
authors: JV
authors: Cassella
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D008152:Loxapine / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged
chemical_list: D014150:Antipsychotic Agents; D008152:Loxapine
keywords: ADASUVE; Staccato; agitation; inhaled loxapine; multiple dose; pharmacodynamics; pharmacokinetics