{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T15:23:24Z","timestamp":1748359404900,"version":"3.40.5"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T00:00:00Z","timestamp":1682467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005595","name":"University of California","doi-asserted-by":"publisher","award":["CCAH grant # 2020\u201020\u2010F"],"award-info":[{"award-number":["CCAH grant # 2020\u201020\u2010F"]}],"id":[{"id":"10.13039\/100005595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The neurosteroid allopregnanolone (ALLO) is under investigation as a treatment for benzodiazepine\u2010refractory status epilepticus (SE). Here, we assess the cardiopulmonary safety of intravenous ALLO by itself and after a clinically recommended dose of midazolam (MDZ) in two healthy adult beagles. Each dog received ALLO (1\u2009mg\/kg, IV), and after a washout period of 2 weeks, each dog was dosed with MDZ (0.2\u2009mg\/kg, IV) followed 10\u2009minutes later by ALLO. Behavioral state, vital signs, arterial blood gases, blood chemistries, and plasma ALLO concentrations were monitored for up to 6\u2009hours after dosing. The dogs appeared sleepy but were fully responsive after both treatments. No depression of mean arterial pressure or respiratory rate was noted. Blood gas measurements failed to show evidence of drug\u2010induced acute respiratory acidosis. Estimated maximum plasma ALLO concentrations were in the range of 1500 to 3000\u2009ng\/ml. The results indicate that intravenous ALLO can be used safely to treat benzodiazepine\u2010refractory SE, even when administered shortly after a benzodiazepine.<\/jats:p>","DOI":"10.1002\/epi4.12723","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T07:40:10Z","timestamp":1678866010000},"page":"666-672","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Tolerability and pharmacokinetics of intravenous allopregnanolone with and without midazolam pretreatment in two healthy dogs"],"prefix":"10.1002","volume":"8","author":[{"given":"Donald A.","family":"Bruun","sequence":"first","affiliation":[{"name":"Department of Molecular Biosciences University of California, Davis (UC Davis) School of Veterinary Medicine  Davis California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Betty","family":"Ma","sequence":"additional","affiliation":[{"name":"Campus Veterinary Services UC Davis, Office of Research  Davis California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi\u2010Je","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology UC Davis School of Medicine  Sacramento California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun\u2010Yi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology UC Davis School of Medicine  Sacramento California USA"},{"name":"UC Davis Bioanalysis and Pharmacokinetics Core Facility UC Davis School of Medicine  Sacramento California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Aleman","sequence":"additional","affiliation":[{"name":"Department of Medicine and Epidemiology UC Davis School of Veterinary Medicine  Davis California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorota","family":"Zolkowska","sequence":"additional","affiliation":[{"name":"Department of Neurology UC Davis School of Medicine  Sacramento California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0201-3270","authenticated-orcid":false,"given":"Suzette M.","family":"Smiley\u2010Jewell","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences University of California, Davis (UC Davis) School of Veterinary Medicine  Davis California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3296-8193","authenticated-orcid":false,"given":"Michael A.","family":"Rogawski","sequence":"additional","affiliation":[{"name":"Department of Pharmacology UC Davis School of Medicine  Sacramento California USA"},{"name":"Department of Neurology UC Davis School of Medicine  Sacramento California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela J.","family":"Lein","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences University of California, Davis (UC Davis) School of Veterinary Medicine  Davis California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,4,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0387-7604(00)00116-9"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12098-011-0505-y"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/vec.12604"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2007.01297.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2018.08.002"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2002.28501.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000009"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/med\/9780199746545.003.0077"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2019.12.001"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2015.03.035"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.14479"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12289"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-198701000-00008"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-198012000-00010"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12917-021-02805-0"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12028-012-9695-z"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13999"},{"key":"e_1_2_9_19_1","unstructured":"FielderSE.Resting heart rates. Merck Veterinary Manual: Reference Guides. Available from:https:\/\/www.merckvetmanual.com\/special\u2010subjects\/reference\u2010guides\/resting\u2010heart\u2010rates. Accessed 28 July 28 2022."},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0195-5616(83)50032-6"},{"key":"e_1_2_9_21_1","unstructured":"Merck.Merck Veterinary Manual: Resting Respiratory Rates. Available from:https:\/\/www.merckvetmanual.com\/multimedia\/table\/resting\u2010respiratory\u2010rates. Accessed 17 August 2022."},{"key":"e_1_2_9_22_1","unstructured":"Zoetis.i\u2010STAT 1 Test Reference Ranges: Canine. Available from:https:\/\/www.zoetisus.com\/products\/diagnostics\/vetscan\/pdf\/i\u2010stat\u20101\u2010cartridge\u2010test\u2010reference\u2010ranges\u2010sellsheet\u2010vts\u201000029.pdf#page=2. 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