{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T17:29:03Z","timestamp":1770485343227,"version":"3.49.0"},"reference-count":22,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,1,22]],"date-time":"2014-01-22T00:00:00Z","timestamp":1390348800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>The objective of this study was to establish effects of inhaled loxapine on the QTc interval in this randomized, placebo\u2010controlled, double\u2010blind crossover study. Forty\u2010eight healthy volunteers received a single inhaled placebo or 10\u2009mg loxapine. Plasma concentrations of loxapine increased with a median Tmax of 1\u2009minute and a mean Cmax of 312\u2009ng\/mL. After an initial rapid distribution phase, plasma concentrations of loxapine declined with a terminal half\u2010life of 8\u2009hours. Exposure to the active metabolite 7\u2010OH\u2010loxapine was 15% of the parent compound based on mean AUC<jats:sub>inf<\/jats:sub> and its terminal half\u2010life was 12\u2009hours. Inhaled loxapine did not increase QT intervals, as demonstrated by the upper bound of the 1\u2010sided 95% CIs placed on the point estimate of the placebo\u2010subtracted change of QTcI (\u0394\u0394QTcI) being less than 10\u2009milliseconds at all 11 post\u2010dose times. The maximum \u0394\u0394QTcI occurred at 1\u2009hour post\u2010dose (LSmean 5.42\u2009milliseconds, upper confidence bound 7.75\u2009milliseconds). The study outcome was validated by the demonstrated assay sensitivity using the positive control moxifloxacin maximum \u0394\u0394QTcI occurred at 3 hour post\u2010dose (LSmean 8.36\u2009milliseconds, lower confidence bound 5.82\u2009milliseconds). The analyses of QTc outliers, and the lack of emergent diagnostic findings for QTcI, QTcB, and QTcF; and simple mean placebo\u2010subtracted changes of QTcI and QTcF supported the primary QT analysis conclusion that this is a negative finding and there is no apparent QT prolongation associated with the therapeutic dose of inhaled loxapine.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcph.257","type":"journal-article","created":{"date-parts":[[2013,12,28]],"date-time":"2013-12-28T11:28:39Z","timestamp":1388230119000},"page":"665-674","source":"Crossref","is-referenced-by-count":23,"title":["Loxapine delivered as a thermally generated aerosol does not prolong QTc in a thorough QT\/QTc study in healthy subjects"],"prefix":"10.1002","volume":"54","author":[{"given":"Daniel A.","family":"Spyker","sequence":"first","affiliation":[{"name":"Alexza Pharmaceuticals, Inc. Mountain View CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Polina","family":"Voloshko","sequence":"additional","affiliation":[{"name":"Cardiocore Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugene R.","family":"Heyman","sequence":"additional","affiliation":[{"name":"Cardiocore Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James V.","family":"Cassella","sequence":"additional","affiliation":[{"name":"Alexza Pharmaceuticals, Inc. Mountain View CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,1,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"198","DOI":"10.2165\/00003495-197815030-00002","article-title":"Loxapine: a review of its pharmacological properties and therapeutic efficacy as an antipsychotic agent","volume":"15","author":"Heel RC","year":"1978","journal-title":"Drugs."},{"key":"e_1_2_7_3_1","first-page":"42","article-title":"Does Loxapine have \u201catypical\u201d properties? Clinical evidence","volume":"60","author":"Glazer WM.","year":"1999","journal-title":"J Clin Psychiatry."},{"key":"e_1_2_7_4_1","unstructured":"International Conference on Harmonisation (ICH) E14 guideline: Clinical Evaluation of QT\/QTc Interval Prolongation and Proarrhythmic Potential for Non\u2010Antiarrhythmic Drugs; October 2005.http:\/\/www.fda.gov\/downloads\/RegulatoryInformation\/Guidances\/ucm129357.pdf."},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270009347866"},{"key":"e_1_2_7_6_1","first-page":"23","article-title":"Parenteral loxapine in severely disturbed schizophrenic patients","volume":"41","author":"Deniker P","year":"1980","journal-title":"J Clin Psychiatry."},{"key":"e_1_2_7_7_1","first-page":"236","article-title":"Parenteral loxapine in acute schizophrenia","volume":"23","author":"O'Connell RA","year":"1978","journal-title":"Current Therapeutic Research."},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004714-198204000-00008"},{"key":"e_1_2_7_9_1","first-page":"172","article-title":"Treatment of acute schizophrenia with loxapine succinate Loxitane in a controlled study with chlorpromazine","volume":"18","author":"Moore DF.","year":"1975","journal-title":"Curr Ther Res Clin Exp."},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1976.tb01492.x"},{"key":"e_1_2_7_11_1","first-page":"361","article-title":"Loxapine succinate: a controlled double\u2010blind study in chronic schizophrenia","volume":"36","author":"Schiele BC.","year":"1975","journal-title":"Dis Nerv Syst."},{"key":"e_1_2_7_12_1","first-page":"175","article-title":"Clinical pharmacological trial of loxapine succinate","volume":"10","author":"Wolpert A","year":"1970","journal-title":"J Clin Pharmacol."},{"key":"e_1_2_7_13_1","first-page":"829","article-title":"Loxapine succinate: a controlled double\u2010blind study in schizophrenia","volume":"16","author":"Charalampous KD","year":"1974","journal-title":"Curr Ther Res Clin Exp."},{"key":"e_1_2_7_14_1","first-page":"594","article-title":"Loxapine: a controlled evaluation in chronic schizophrenic patients","volume":"12","author":"Bishop MP","year":"1970","journal-title":"Curr Ther Res Clin Exp."},{"key":"e_1_2_7_15_1","first-page":"7","article-title":"Evaluation of two dose levels of loxapine succinate in chronic schizophrenia","volume":"38","author":"Clark ML","year":"1977","journal-title":"Dis Nerv Syst."},{"key":"e_1_2_7_16_1","first-page":"656","article-title":"Parenteral and oral loxitane in the treatment of schizophrenic disorders","volume":"31","author":"Cole JO","year":"1982","journal-title":"Current Therapeutic Research."},{"key":"e_1_2_7_17_1","first-page":"777","article-title":"Efficacy of Loxapine administered parenterally and orally to acute and chronic schizophrenic patients","volume":"28","author":"Denber HCB.","year":"1980","journal-title":"Current Therapeutic Research."},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.1978.tb02400.x"},{"key":"e_1_2_7_19_1","first-page":"301","article-title":"A double\u2010blind comparison of loxitane\u2013loxapine succinate and trifluoperazine hydrochloride in chronic schizophrenic patients","volume":"36","author":"Moyano CZ.","year":"1975","journal-title":"Dis Nerv Syst."},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.138.8.1089"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8167.1999.tb00224.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(02)02074-5"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.320.7243.1158"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcph.257","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.257","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.257","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.257","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T07:53:51Z","timestamp":1696492431000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,22]]},"references-count":22,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2014,6]]}},"alternative-id":["10.1002\/jcph.257"],"URL":"https:\/\/doi.org\/10.1002\/jcph.257","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,22]]}}}