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After a 2\u2010day placebo run\u2010in phase, healthy male volunteers received placebo or asenapine escalated to dosages of 3, 5, 10, or 15 mg bid. Another group received single doses (2 and 5 mg) 1 week apart. Serial blood samples were obtained for pharmacokinetic analysis. The single asenapine doses and multiple bid doses up to 10 mg were well tolerated. The most frequent treatment\u2010emergent adverse events were somnolence, oral paresthesia, fatigue, headache, dizziness, and dyspnea. Clinically relevant abnormalities or trends in laboratory and vital signs measures, physical examinations, or electrocardiograms were not observed. Asenapine was rapidly absorbed, with a t<jats:sub>max<\/jats:sub> of \u223c1 hour, and was biphasically eliminated with a terminal elimination half\u2010life of 20 to 30 hours. In the range of 3 to 10 mg bid, increases in plasma concentrations were less than dose proportional. Asenapine appears to be well tolerated at single doses up to 5 mg and multiple doses up to 10 mg bid and can be administered to healthy volunteers in clinical pharmacology studies using the dosing regimens described.<\/jats:p>","DOI":"10.1177\/2160763x12455328","type":"journal-article","created":{"date-parts":[[2012,9,12]],"date-time":"2012-09-12T21:24:53Z","timestamp":1347485093000},"page":"131-143","source":"Crossref","is-referenced-by-count":5,"title":["Asenapine Safety, Tolerability, and Pharmacokinetics After Single and Multiple Doses in Healthy Volunteers"],"prefix":"10.1002","volume":"1","author":[{"given":"Peter","family":"Dogterom","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cees","family":"Timmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rik","family":"de Greef","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edwin","family":"Spaans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dick","family":"de Vries","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andre","family":"van Vliet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Peeters","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,1,10]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/10401230701334606"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.64.4.442"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v68n0303"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.2006.00887.x"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1517\/14740330802423234"},{"key":"e_1_2_7_7_2","unstructured":"Reuters. 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