{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T22:45:23Z","timestamp":1759963523544},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,3,7]],"date-time":"2013-03-07T00:00:00Z","timestamp":1362614400000},"content-version":"vor","delay-in-days":310,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:p>Asenapine is indicated for treatment of schizophrenia in the United States and acute treatment of manic or mixed episodes, as monotherapy (United States and European Union) or adjunct therapy (United States only), associated with bipolar I disorder. It is extensively metabolized; the 2 main metabolites are asenapine N\u2010glucuronide and N\u2010desmethyl\u2010asenapine. The authors investigated the pharmacokinetic interactions between asenapine and valproate in an open\u2010label, randomized, 2\u2010way crossover study. Twenty\u2010four healthy male volunteers received sublingual doses of asenapine 5 mg alone or under steady\u2010state valproate (500 mg bid for 9 days). Blood samples collected until 72 hours postdosing were analyzed for asenapine, N\u2010desmethyl\u2010asenapine, and asenapine N\u2010glucuronide. Compared with asenapine alone, valproate substantially reduced N\u2010glucuronide formation (area under the curve from 0 to infinity [AUC<jats:sub>0\u2010\u221e<\/jats:sub>] reduced 7.4\u2010fold, maximum concentration [C<jats:sub>max<\/jats:sub>] reduced 6.6\u2010fold) and moderately reduced N\u2010desmethyl\u2010asenapine formation (AUC<jats:sub>0\u2010\u221e<\/jats:sub> reduced 30%, C<jats:sub>max<\/jats:sub> unchanged). Coadministration of valproate did not affect asenapine AUC<jats:sub>0\u2010\u221e<\/jats:sub> and C<jats:sub>max<\/jats:sub> (confidence intervals for the ratios of asenapine AUC<jats:sub>0\u2010\u221e<\/jats:sub> and C<jats:sub>max<\/jats:sub> were contained within the predefined 0.80\u20131.25 acceptance range). Low\u2010dose valproate, although almost completely inhibiting glucuronidation of asenapine, did not affect the pharmacokinetics of asenapine itself, the entity primarily responsible for the pharmacologic effects of the drug.<\/jats:p>","DOI":"10.1177\/0091270011404028","type":"journal-article","created":{"date-parts":[[2011,6,1]],"date-time":"2011-06-01T02:22:59Z","timestamp":1306894979000},"page":"757-765","source":"Crossref","is-referenced-by-count":17,"title":["Valproate Reduces the Glucuronidation of Asenapine Without Affecting Asenapine Plasma Concentrations"],"prefix":"10.1002","volume":"52","author":[{"given":"Mireille G.F.","family":"Gerrits","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rik","family":"de Greef","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Dogterom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre A.M.","family":"Peeters","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,3,7]]},"reference":[{"key":"e_1_2_5_2_2","volume-title":"Saphris (asenapine sublingual tablets) [full prescribing information]","year":"2010"},{"key":"e_1_2_5_3_2","unstructured":"European Medicines Agency. 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