Pharmacokinetics of loxapine following inhalation of a thermally generated aerosol in healthy volunteers.
The objective of this randomized, double-blind, placebo-controlled, dose escalation study was to determine the pharmacokinetic characteristics, safety, and tolerability of single doses of inhaled loxapine aerosol in healthy volunteers. Loxapine was delivered by means of a unique thermally generated aerosol comprising drug particles of a size designed for deep lung delivery and absorption. Fifty participants were randomized to receive 0.625, 1.25, 2.5, 5.0, or 10 mg of loxapine aerosol or placebo. Following inhalation, the t(max) median (25%, 75%) was 2 (1, 3) minutes. The loxapine AUC(infinity) was dose proportional across all doses with slope (90% confidence interval) of log AUC(infinity) versus log dose = 0.909 (0.832, 0.987). No clinically meaningful changes were noted in hematology results, blood chemistry, vital signs, or respiratory function. The most common adverse events were dizziness, somnolence, and bad taste. The inhalation of Staccato loxapine represents a safe, well-tolerated means for rapidly achieving therapeutic plasma concentrations of loxapine.
Spyker
Daniel A
DA
Alexza Pharmaceuticals, Inc, Mountain View, CA 94043, USA. dspyker@alexza.com
Munzar
Patrik
P
Cassella
James V
JV
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008152:Loxapine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D018492:Dopamine Antagonists; D008152:Loxapine