Cargando…

Multiple dose pharmacokinetics of inhaled loxapine in subjects on chronic, stable antipsychotic regimens

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 uniq...

Descripción completa

Detalles Bibliográficos
Autores principales: Spyker, Daniel A., Riesenberg, Robert A., Cassella, James V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029575/
https://www.ncbi.nlm.nih.gov/pubmed/25808074
http://dx.doi.org/10.1002/jcph.502
_version_ 1782454532653973504
author Spyker, Daniel A.
Riesenberg, Robert A.
Cassella, James V.
author_facet Spyker, Daniel A.
Riesenberg, Robert A.
Cassella, James V.
author_sort Spyker, Daniel A.
collection PubMed
description 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 T(max) was 2 minutes, and concentrations declined to about half C(max) 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 AUC(inf) 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
format Online
Article
Text
id pubmed-5029575
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-50295752016-10-03 Multiple dose pharmacokinetics of inhaled loxapine in subjects on chronic, stable antipsychotic regimens Spyker, Daniel A. Riesenberg, Robert A. Cassella, James V. J Clin Pharmacol Editor's Choice: Pharmacokinetics 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 T(max) was 2 minutes, and concentrations declined to about half C(max) 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 AUC(inf) 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 John Wiley and Sons Inc. 2015-09 2015-05-06 /pmc/articles/PMC5029575/ /pubmed/25808074 http://dx.doi.org/10.1002/jcph.502 Text en © 2015 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Editor's Choice: Pharmacokinetics
Spyker, Daniel A.
Riesenberg, Robert A.
Cassella, James V.
Multiple dose pharmacokinetics of inhaled loxapine in subjects on chronic, stable antipsychotic regimens
title Multiple dose pharmacokinetics of inhaled loxapine in subjects on chronic, stable antipsychotic regimens
title_full Multiple dose pharmacokinetics of inhaled loxapine in subjects on chronic, stable antipsychotic regimens
title_fullStr Multiple dose pharmacokinetics of inhaled loxapine in subjects on chronic, stable antipsychotic regimens
title_full_unstemmed Multiple dose pharmacokinetics of inhaled loxapine in subjects on chronic, stable antipsychotic regimens
title_short Multiple dose pharmacokinetics of inhaled loxapine in subjects on chronic, stable antipsychotic regimens
title_sort multiple dose pharmacokinetics of inhaled loxapine in subjects on chronic, stable antipsychotic regimens
topic Editor's Choice: Pharmacokinetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029575/
https://www.ncbi.nlm.nih.gov/pubmed/25808074
http://dx.doi.org/10.1002/jcph.502
work_keys_str_mv AT spykerdaniela multipledosepharmacokineticsofinhaledloxapineinsubjectsonchronicstableantipsychoticregimens
AT riesenbergroberta multipledosepharmacokineticsofinhaledloxapineinsubjectsonchronicstableantipsychoticregimens
AT cassellajamesv multipledosepharmacokineticsofinhaledloxapineinsubjectsonchronicstableantipsychoticregimens