{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T08:29:54Z","timestamp":1769761794806,"version":"3.49.0"},"reference-count":11,"publisher":"Wiley","issue":"5-6","license":[{"start":{"date-parts":[[2010,6,15]],"date-time":"2010-06-15T00:00:00Z","timestamp":1276560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2010,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Asenapine is a psychopharmacologic agent approved in the United States for the acute treatment of schizophrenia in adults and the acute treatment of manic or mixed episodes associated with bipolar I disorder with or without psychotic features in adults. It is pending approval for the treatment of schizophrenia and manic episodes associated with bipolar I disorder in Europe. Asenapine is administered as a sublingual formulation. To determine whether the pharmacokinetics of asenapine are impacted by placing the tablet buccally (\u2018cheeking\u2019) or allowing the tablet to dissolve on the top of the tongue, pharmacokinetics were compared following buccal and supralingual administration versus sublingual administration. In this open\u2010label, randomized, 3\u2010way crossover trial, healthy men (<jats:italic>n<\/jats:italic>=36) received single 5 mg doses of asenapine via sublingual, supralingual and buccal routes, at least 1 week apart. With buccal administration, the area under the concentration\u2010over\u2010time curve (<jats:italic>AUC<\/jats:italic><jats:sub>0\u2013\u221e<\/jats:sub>) and peak concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) were, respectively, 24%, and 19% higher than with sublingual administration; these routes were not bioequivalent. With supralingual administration, <jats:italic>AUC<\/jats:italic><jats:sub>0\u2013\u221e<\/jats:sub> and <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> were 6% and 13% lower than with sublingual administration; bioequivalence was established based on <jats:italic>AUC<\/jats:italic><jats:sub>0\u2013\u221e<\/jats:sub> only; bioequivalence based on <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> could not be assessed due to 40% within\u2010subject variability. The most common adverse events were oral paresthesia (sublingual, 75.8%; supralingual, 55.9%; buccal, 45.7%) and somnolence (81.8%; 76.5%; 68.6%). Compared with the recommended sublingual route of asenapine administration, exposure was 24% higher with buccal administration and comparable to supralingual administration. However, differences in exposure associated with variable placement in the oral cavity did not compromise safety in healthy subjects. Copyright \u00a9 2010 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/bdd.718","type":"journal-article","created":{"date-parts":[[2010,6,15]],"date-time":"2010-06-15T08:07:25Z","timestamp":1276589245000},"page":"351-357","source":"Crossref","is-referenced-by-count":25,"title":["Effect of absorption site on the pharmacokinetics of sublingual asenapine in healthy male subjects"],"prefix":"10.1002","volume":"31","author":[{"given":"Mireille","family":"Gerrits","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rik","family":"de Greef","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":[[2010,6,25]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.schbul.a007076"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2006.00314.x"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.pra.0000265764.87376.02"},{"issue":"1","key":"e_1_2_1_5_2","first-page":"S86","article-title":"A phase I study to investigate the safety, tolerability, and pharmacokinetics of single and multiple doses of sublingually administered asenapine in healthy male volunteers","volume":"85","author":"Dogterom P","year":"2009","journal-title":"Clin Pharmacol Ther"},{"issue":"1","key":"e_1_2_1_6_2","first-page":"S86","article-title":"Effects of water intake and smoking on absorption of sublingually administered asenapine","volume":"85","author":"Hulskotte EGJ","year":"2009","journal-title":"Clin Pharmacol Ther"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.2510140503"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/20.6.369"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200645070-00009"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.2165\/00044011-200828010-00001"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2009.44"},{"key":"e_1_2_1_12_2","unstructured":"de GreefR FribergLE ChapelS et al. Modeling and simulation to integrate efficacy and safety data following full development: a case study in schizophrenia and bipolar disorder. Presented at: Population Approach Group in Europe; 18\u201320 June2008; Marseille France (abstract available at:http:\/\/www.page\u2010meeting.org\/default.asp?abstract=1274)."}],"container-title":["Biopharmaceutics &amp; Drug Disposition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdd.718","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdd.718","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T11:56:04Z","timestamp":1693396564000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdd.718"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,6,25]]},"references-count":11,"journal-issue":{"issue":"5-6","published-print":{"date-parts":[[2010,7]]}},"alternative-id":["10.1002\/bdd.718"],"URL":"https:\/\/doi.org\/10.1002\/bdd.718","archive":["Portico"],"relation":{},"ISSN":["0142-2782","1099-081X"],"issn-type":[{"value":"0142-2782","type":"print"},{"value":"1099-081X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,6,25]]}}}