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Pharmacokinetics of Loxapine Following Inhalation of a Thermally Generated Aerosol in Healthy Volunteers
Author(s) -
Spyker Daniel A.,
Munzar Patrik,
Cassella James V.
Publication year - 2010
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009347866
Subject(s) - pharmacokinetics , medicine , tolerability , inhalation , anesthesia , placebo , adverse effect , confidence interval , pharmacology , alternative medicine , pathology
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 ∞ was dose proportional across all doses with slope (90% confidence interval) of log AUC ∞ 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.