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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2015
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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 |
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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 |
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