{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T10:46:12Z","timestamp":1761821172091},"reference-count":20,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,3,8]],"date-time":"2013-03-08T00:00:00Z","timestamp":1362700800000},"content-version":"vor","delay-in-days":3141,"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":[[2004,8]]},"abstract":"<jats:p>This was a double\u2010blind, randomized, placebo\u2010controlled study to investigate rising oral doses of BIA 2\u2010093 (S\u2010(\u2212)\u201010\u2010acetoxy\u201010,11\u2010dihydro\u20105H\u2010dibenz\/b,f\/azepine\u20105\u2010carboxamide), a putative new antiepileptic drug. Within each of 4 dosage groups of 8 healthy male adult subjects, 2 subjects were randomized to receive placebo, and the remaining 6 subjects were randomized to receive BIA 2\u2010093 (200 mg bid, 400 mg qd, 800 mg qd, and 1200 mg qd) for 8 days. Concentrations of BIA 2\u2010093 in plasma or urine were generally not measurable. Median maximum plasma concentrations of the major metabolite (licarbazepine, (\u00b1)\u201010,11\u2010dihydro\u201010\u2010hydroxy\u20105H\u2010dibenz\/b,f\/azepine\u20105\u2010carboxamide) were attained (t<jats:sub><jats:italic>max<\/jats:italic><\/jats:sub>) at 2 to 3 h postdose; thereafter, plasma concentrations declined with a mean apparent terminal half\u2010life of 9 to 13 h following repeated dosing. The extent of systemic exposure to licarbazepine increased in an approximately dose\u2010proportional manner following single and repeated administration. Licarbazepine accumulated in plasma following repeated administration of BIA 2\u2010093; the mean extent of accumulation (R<jats:sub><jats:italic>O<\/jats:italic><\/jats:sub>, calculated from AUC<jats:sub><jats:italic>0\u2010\u03c4<\/jats:italic><\/jats:sub> (day 8)\/AUC<jats:sub><jats:italic>0\u2010\u03c4<\/jats:italic><\/jats:sub> (day 1)) was 3.0 after repeated, twice\u2010daily dosing and 1.4 to 1.7 after once\u2010daily dosing. Steady\u2010state plasma licarbazepine concentrations were attained at 4 to 5 days of once\u2010 or twice\u2010daily dosing, consistent with an effective half\u2010life on the order of 20 to 24 h. The mean renal clearance of licarbazepine from plasma was approximately 20 to 30 mL\/min, which is low compared with the glomerular filtration rate. The total amount of licarbazepine recovered in urine was approximately 20% within 12 h postdose and 40% within 24 h postdose. All adverse events were mild in severity, except for 1 case of somnolence of moderate severity, which occurred in a subject receiving 1200 mg BIA 2\u2010093. The incidence of adverse events was similar between all treatment groups, including placebo. There were no serious adverse events. In conclusion, BIA 2\u2010093 was well tolerated and appeared to be rapidly and extensively metabolized to licarbazepine following single and repeated administration to healthy young subjects.<\/jats:p>","DOI":"10.1177\/0091270004267591","type":"journal-article","created":{"date-parts":[[2004,7,15]],"date-time":"2004-07-15T01:32:39Z","timestamp":1089855159000},"page":"906-918","source":"Crossref","is-referenced-by-count":51,"title":["Safety, Tolerability, and Pharmacokinetic Profile of BIA 2\u2010093, a Novel Putative Antiepileptic, in a Rising Multiple\u2010Dose Study in Young Healthy Humans"],"prefix":"10.1002","volume":"44","author":[{"given":"Luis","family":"Almeida","sequence":"first","affiliation":[]},{"given":"Patr\u00edcio","family":"Soares\u2010da\u2010Silva","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2013,3,8]]},"reference":[{"key":"e_1_2_5_2_2","first-page":"821","volume-title":"The Treatment of Epilepsy: Principles and Practice","author":"Sillanp\u00e4\u00e4 ML","year":"2001"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1980.tb04081.x"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.33.7.904"},{"key":"e_1_2_5_5_2","first-page":"236","volume-title":"Antiepileptic Drugs","author":"Spina E","year":"2002"},{"key":"e_1_2_5_6_2","first-page":"295","volume-title":"Advances in Epileptology 1977","author":"Baltzer V","year":"1978"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(95)02014-4"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1987.tb03702.x"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm980627g"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(01)00231-5"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1014814924965"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(01)00584-6"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-0186(01)00101-2"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2001.43600.x"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.2165\/00126839-200304050-00001"},{"key":"e_1_2_5_16_2","first-page":"290","volume-title":"Advances in Epileptology","author":"Feldmann KF","year":"1978"},{"key":"e_1_2_5_17_2","first-page":"89","volume-title":"Advances in Epileptology: XIIth Epilepsy International Symposium","author":"Feldmann KF","year":"1981"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1155\/1990\/917164"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.3109\/00498258609043567"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4347(92)80459-4"},{"key":"e_1_2_5_21_2","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1053\/cp.1999.v66.103170001","article-title":"Enantioselective pharmacokinetics of 10\u2010hydroxycarbazepine after oral administration of oxcarbazepine to healthy Chinese subjects","volume":"66","author":"Volosov A","year":"1999","journal-title":"Clin Pharmacol Ther"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1177%2F0091270004267591","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1177\/0091270004267591","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T11:11:04Z","timestamp":1697109064000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1177\/0091270004267591"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,8]]},"references-count":20,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2004,8]]}},"alternative-id":["10.1177\/0091270004267591"],"URL":"https:\/\/doi.org\/10.1177\/0091270004267591","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,8]]}}}