{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T10:08:43Z","timestamp":1759226923147},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,9,20]],"date-time":"2016-09-20T00:00:00Z","timestamp":1474329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Intramuscular droperidol is used increasingly for sedation of aggressive and violent patients. This study aimed to characterise the pharmacokinetics of intramuscular droperidol in these patients to determine how rapidly it is absorbed and the expected duration of measurable drug concentrations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We undertook a population pharmacokinetic analysis of a subgroup of patients from a clinical trial comparing droperidol and midazolam: 17 receiving 5\u00a0mg and 24 receiving 10\u00a0mg droperidol. Droperidol was measured using high\u2010performance liquid chromatography. Pharmacokinetic modelling was performed under a nonlinear mixed effects modelling framework (NONMEM v7.2). The model was used to simulate concentration time profiles of three typical doses, 5\u00a0mg, 10\u00a0mg and 10\u00a0mg\u00a0+\u00a010\u00a0mg repeated at 15\u00a0min.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A two\u2010compartment first\u2010order input with first\u2010order output model fitted the data best. The absorption rate constant was poorly characterised by the data and an estimate of the first order rate constant of absorption when fixed to 10\u00a0h<jats:sup>\u20131<\/jats:sup> provided a stable model and lowest objective function. This represents extremely rapid absorption with a half\u2010life of 5\u00a0min. The final model had a clearance of 41.9\u00a0l\u00a0h<jats:sup>\u20131<\/jats:sup> and volume of distribution of the central compartment of, 73.6\u00a0l. Median and interquartile range of initial (alpha) half\u2010life was 0.32\u00a0h (0.26\u20130.37\u00a0h) and second (beta) half\u2010life was 3.0\u00a0h (2.5\u20133.6\u00a0h). Simulations indicate that 10\u00a0mg alone provides an 80% probability of being above the lower limit of quantification (5\u00a0\u03bcg\u00a0l<jats:sup>\u20131<\/jats:sup>) for 7\u00a0h, 2\u00a0h longer than for 5\u00a0mg. Giving two 10\u00a0mg doses increased this duration to 10\u00a0h.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Intramuscular droperidol is rapidly absorbed with high therapeutic concentrations after 5 and 10\u00a0mg doses, and supports clinical data in which droperidol sedates rapidly for up to 6\u00a0h.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13093","type":"journal-article","created":{"date-parts":[[2016,8,17]],"date-time":"2016-08-17T02:56:39Z","timestamp":1471402599000},"page":"1550-1556","source":"Crossref","is-referenced-by-count":9,"title":["Population pharmacokinetics of intramuscular droperidol in acutely agitated patients"],"prefix":"10.1111","volume":"82","author":[{"given":"Lee\u2010Kien","family":"Foo","sequence":"first","affiliation":[{"name":"School of Pharmacy University of Otago  Dunedin New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen B.","family":"Duffull","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Otago  Dunedin New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonie","family":"Calver","sequence":"additional","affiliation":[{"name":"Clinical Toxicology Research Group University of Newcastle  New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Schneider","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy University of Newcastle  New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey K.","family":"Isbister","sequence":"additional","affiliation":[{"name":"Clinical Toxicology Research Group University of Newcastle  New South Wales Australia"},{"name":"Department of Clinical Toxicology and Pharmacology Calvary Mater Newcastle  Newcastle New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,9,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1037"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-227X-10-14"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-6723.2009.01182.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1197\/j.aem.2005.07.017"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annemergmed.2005.07.003"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.114.150227"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annemergmed.2010.05.037"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/10903120590891723"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1197\/aemj.9.12.1402"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-0644(05)82660-5"},{"key":"e_1_2_9_12_1","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1213\/00000539-199306000-00010","article-title":"The pharmacokinetics of droperidol in anesthetized children","volume":"76","author":"Grunwald Z","year":"1993","journal-title":"Anesth Analg"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1015822715190"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/61.3.297"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-197304000-00010"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0920-1211(91)90011-4"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annemergmed.2015.03.016"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annemergmed.2012.07.118"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/00063110-199709000-00003"},{"key":"e_1_2_9_20_1","volume-title":"POPT \u2010 Installation and user guide","author":"Duffull SB","year":"2006"},{"key":"e_1_2_9_21_1","volume-title":"NONMEM User's Guides. 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