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In 2 cohorts (7\u20108 PF\u201006372865 and 2 placebo in each cohort), healthy adult subjects received twice\u2010daily oral doses of PF\u201006372865 for 21 days, which included titration in the first 7 days, followed by a maintenance dose of 25\u00a0mg twice daily (Cohort 1) and 42.5\u00a0mg twice daily (Cohort 2) for 14 days. Serial PK samples were collected on days 1 and 21. Nineteen subjects were assigned to study treatments; 18 completed the study. Approximate dose\u2010proportional increases in maximum plasma concentratin and area under the plasma concentration\u2013time curve over the dosing interval were observed. PF\u201006372865 was rapidly absorbed with a median time to maximum concentration of 1 to 2 hours following both single\u2010 and multiple\u2010dose administration. Mean terminal elimination half\u2010life on day 21 was approximately 11 hours in both cohorts. All adverse events were mild; the most frequently reported was dizziness. After titration, there were no reports of somnolence. There were no clinically significant safety findings, including a lack of withdrawal symptoms on discontinuation of treatment. These results demonstrate that PF\u201006372865 is safe and well tolerated at doses estimated to achieve high receptor occupancy (&gt;80%), a profile differentiated from nonselective benzodiazepines.<\/jats:p>","DOI":"10.1002\/cpdd.912","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T20:21:28Z","timestamp":1611087688000},"page":"756-764","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Safety, Tolerability, and Pharmacokinetics of Multiple Repeated Oral Doses of the \u03b12\/3\/5\u2010Subtype Selective GABA<sub>A<\/sub>\u2010Positive Allosteric Modulator PF\u201006372865 in Healthy Volunteers"],"prefix":"10.1002","volume":"10","author":[{"given":"Rachel","family":"Gurrell","sequence":"first","affiliation":[{"name":"Cerevel Therapeutics LLC  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Whitlock","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  Granta Park Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Wei","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongzhou","family":"Shen","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Ogden","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  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