{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T03:03:48Z","timestamp":1782788628990,"version":"3.54.5"},"reference-count":22,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,5,28]],"date-time":"2017-05-28T00:00:00Z","timestamp":1495929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2017,5,28]],"date-time":"2017-05-28T00:00:00Z","timestamp":1495929600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Lack of non\u2010injectable naloxone formulations has impeded widespread take\u2010home provision for the prevention of heroin\/opioid overdose deaths. For non\u2010injectable formulations that are finally being investigated, rapid onset of action and sufficient bioavailability will be vital. We present analysis of data from a study of concentrated naloxone nasal spray formulations. Our aims are: to assess (1) pharmacokinetic properties and (2) suitability for overdose reversal in terms of naloxone absorption within 30\u00a0minutes post\u2010dosing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design and interventions\/comparator<\/jats:title>\n                    <jats:p>Open\u2010label, randomized, four\u2010way cross\u2010over Latin\u2010square pharmacokinetic study of naloxone administration by three routes: intranasal at two doses (8\u00a0mg\/0.4\u00a0ml, 16\u00a0mg\/0.4\u00a0ml) versus sublingual (16\u00a0mg\/ml) versus intravenous reference (1\u00a0mg\/ml).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Clinical Pharmacology Unit at The Ohio State University (Columbus, OH, USA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>Twelve healthy volunteers (age 20\u201341; seven female).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements<\/jats:title>\n                    <jats:p>\n                      From blood plasma naloxone concentrations, (1) standard pharmacokinetic parameters, including maximum plasma concentration (C\n                      <jats:sub>max<\/jats:sub>\n                      ) and mean absolute bioavailability (\n                      <jats:italic>F<\/jats:italic>\n                      %, relative to intravenous injection), were determined; as well as (2) partial area under the curve (AUC) values,\n                      <jats:italic>t<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      (time to maximum plasma concentration) and\n                      <jats:italic>t<\/jats:italic>\n                      <jats:sub>50%<\/jats:sub>\n                      (time to 50% of maximum plasma concentration) as measures of early absorption.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>\n                      (1) Bioavailability was\n                      <jats:italic>F<\/jats:italic>\n                      %\u00a0=\u00a025\u201328% for intranasal naloxone. Sublingual had low bioavailability (\n                      <jats:italic>F<\/jats:italic>\n                      %\u00a0=\u00a02%) and was not considered further. Mean C\n                      <jats:sub>max<\/jats:sub>\n                      values for 8\u00a0mg (12.83\u00a0ng\/ml) and 16\u00a0mg (18.25\u00a0ng\/ml) intranasal exceeded 1\u00a0mg intravenous (9.64\u00a0ng\/ml) naloxone. (2) Following intranasal administration,\n                      <jats:italic>t<\/jats:italic>\n                      <jats:sub>50%<\/jats:sub>\n                      was reached within 8\u00a0minutes and\n                      <jats:italic>t<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      within 20\u00a0minutes. Mean naloxone absorption from dosing to 30\u00a0minutes (AUC\n                      <jats:sub>30<\/jats:sub>\n                      ) was greater following 8\u00a0mg (4.17\u00a0h\u00a0\u00d7\u00a0ng\/ml) and 16\u00a0mg (5.91\u00a0h\u00a0\u00d7\u00a0ng\/ml) intranasal than following 1\u00a0mg intravenous (1.70\u00a0h\u00a0\u00d7\u00a0ng\/ml) administration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Concentrated naloxone nasal spray has a promising pharmacokinetic profile, with substantial bioavailability. Its early absorption time\u2013course suggests that concentrated nasal naloxone is suitable for emergency administration in the community, where rapid restoration of respiratory function is essential for opioid overdose reversal.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/add.13849","type":"journal-article","created":{"date-parts":[[2017,4,21]],"date-time":"2017-04-21T09:11:55Z","timestamp":1492765915000},"page":"1647-1652","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Pharmacokinetics of concentrated naloxone nasal spray over first 30\u00a0minutes post\u2010dosing: analysis of suitability for opioid overdose reversal"],"prefix":"10.1111","volume":"112","author":[{"given":"Gill","family":"Mundin","sequence":"first","affiliation":[{"name":"Mundipharma Research Limited  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"McDonald","sequence":"additional","affiliation":[{"name":"National Addiction Centre Institute of Psychiatry, Psychology and Neuroscience, King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Smith","sequence":"additional","affiliation":[{"name":"Mundipharma Research Limited  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Clinical Research Purdue Pharma LP  Stamford CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Strang","sequence":"additional","affiliation":[{"name":"National Addiction Centre Institute of Psychiatry, Psychology and Neuroscience, King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,5,28]]},"reference":[{"key":"e_1_2_6_2_1","volume-title":"Opioid Overdose: Preventing and Reducing Opioid Overdose Mortality","author":"United Nations Office on Drugs and Crime\/World Health Organization (ODC\/WHO)","year":"2013"},{"key":"e_1_2_6_3_1","volume-title":"Naloxone for Outpatient Use: Data Required to Support an NDA","author":"Hertz S.","year":"2012"},{"key":"e_1_2_6_4_1","unstructured":"Food and Drug Administration (FDA).FDA moves quickly to approve easy\u2010to\u2010use nasal spray to treat opioid overdose.2015. 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