{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T12:22:42Z","timestamp":1768479762390,"version":"3.49.0"},"reference-count":13,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,5,15]],"date-time":"2018-05-15T00:00:00Z","timestamp":1526342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Strongbridge Biopharma"},{"name":"Taro Pharmaceuticals"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Single\u2010and multiple\u2010dose pharmacokinetics and safety were investigated in this phase 1 study of dichlorphenamide, a carbonic anhydrase inhibitor approved in the United States for treatment of primary periodic paralysis. Dichlorphenamide was administered to 6 cohorts (n = 6 each) of healthy adults. Cohorts A through E received single doses of 25\u2013400 mg followed by 50\u2013800 mg\/day in divided doses for 10 total doses. Cohort F (safety analysis only) received up to 28 titrated doses from 100\u2013800 mg\/day. Plasma for pharmacokinetics sampling was obtained predose and up to 48 hours postdose. Twenty\u2010five of 36 enrolled subjects completed.\u00a0Median time to maximum plasma concentration ranged from 1.5\u20133 hours, and mean half\u2010life from 32\u201368 hours. Mean area under the concentration\u2010time curve from time 0 to tau (length of the dosing interval estimated using the trapezoidal method) and maximum observed plasma concentration increased dose\u2010proportionally after multiple doses. The incidence and severity of adverse events (AEs) were dose\u2010related, with at least one mild AE reported among 17%, 17%, and 67% of patients in cohorts A, B, and C, respectively; and at least one mild\u2010to\u2010moderate AE among 100% of subjects in cohorts D, E, and F.\u00a0One serious AE of rash was reported in cohort F. Eleven subjects discontinued; 10 due to AEs at 400 or 800 mg\/day (cohorts E and F), including 100% of cohort F. Hypokalemia contributed to 5 of 6 discontinuations in cohort F (all 800 mg\/day).<\/jats:p>","DOI":"10.1002\/cpdd.464","type":"journal-article","created":{"date-parts":[[2018,5,15]],"date-time":"2018-05-15T14:56:10Z","timestamp":1526396170000},"page":"87-94","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Open\u2010Label, Dose\u2010Escalation, Phase 1 Study of Safety and Single and Multiple\u2010Dose Pharmacokinetics of Dichlorphenamide in Healthy Volunteers"],"prefix":"10.1002","volume":"8","author":[{"given":"Fredric","family":"Cohen","sequence":"first","affiliation":[{"name":"Strongbridge Biopharma plc  Trevose PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,5,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c140062"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2660(08)01001-8"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2011.00008"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31823a0cb6"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002416"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200001)47:1<46::AID-ANA9>3.0.CO;2-H"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-016-0559-2"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.289.6441.347"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.054999"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.2014.897328"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM195305212482102"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM195405062501803"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/58.5.512"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcpdd.464","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.464","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T18:54:49Z","timestamp":1694285689000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.464"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,15]]},"references-count":13,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,1]]}},"alternative-id":["10.1002\/cpdd.464"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.464","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,15]]},"assertion":[{"value":"2017-10-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-02-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}