{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T17:16:46Z","timestamp":1716830206038},"reference-count":10,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2008,6,28]],"date-time":"2008-06-28T00:00:00Z","timestamp":1214611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Archives of Drug Info"],"published-print":{"date-parts":[[2008,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:bold>Objective.\u2002<\/jats:bold> This study was conducted to assess the dose proportionality, safety, and tolerability of fentanyl buccal tablet (FBT) in Japanese volunteers.<\/jats:p><jats:p><jats:bold>Methods.\u2002<\/jats:bold> Healthy, opioid\u2010naive Japanese adults received single\u2010dose FBT 100, 200, 400, and 800\u2003\u00b5g in a randomized, open\u2010label, crossover fashion. Naltrexone was given to minimize the opioid effects of fentanyl. Peak serum fentanyl concentration (C<jats:sub>max<\/jats:sub>), time to C<jats:sub>max<\/jats:sub> (t<jats:sub>max<\/jats:sub>), area under the serum fentanyl concentration\u2010time curve (AUC) from time 0 to infinity (AUC<jats:sub>0\u2013\u221e<\/jats:sub>), and AUC from 0 to the last quantifiable concentration (AUC<jats:sub>0\u2013last<\/jats:sub>) were summarized using descriptive statistics. Dose proportionality was claimed if the ln\u2010ln plots of C<jats:sub>max<\/jats:sub>, AUC<jats:sub>0\u2013\u221e<\/jats:sub>, and AUC<jats:sub>0\u2013last<\/jats:sub> vs. dose were linear and the 90% confidence intervals (CI) of the slopes were within 0.8927 and 1.1073. The safety population comprised volunteers who received \u22651 FBT.<\/jats:p><jats:p><jats:bold>Results.\u2002<\/jats:bold> Twenty\u2010five volunteers were enrolled, 23 were included in the safety population (mean age 35.3 years), and 19 completed the study. The assessment of dose proportionality did not meet the statistical criteria (slope [90% CI]: 0.9118 [0.8601, 0.9635] for C<jats:sub>max<\/jats:sub>, 1.0756 [1.0377, 1.1136] for AUC<jats:sub>0\u2013\u221e<\/jats:sub>, and 1.0992 [1.0677, 1.1307] for AUC<jats:sub>0\u2013last<\/jats:sub>). However, the increase in systemic exposure with dose appeared linear, and a post hoc analysis of partial AUCs from time 0 to 8, 12, 18, and 24 hours supported dose proportionality. Median t<jats:sub>max<\/jats:sub> of 90 minutes (range 30\u2013180 minutes) was independent of dose. Adverse events (AEs) were mild or moderate. The most frequent AEs were nausea (N\u2003=\u20039), dizziness (N\u2003=\u20038), headache (N\u2003=\u20036), somnolence (N\u2003=\u20036), dyspepsia (N\u2003=\u20035), and vomiting (N\u2003=\u20033). No application\u2010site or serious AEs were reported.<\/jats:p><jats:p><jats:bold>Conclusions.\u2002<\/jats:bold> Systemic exposure to FBT was approximately dose proportional across the range 100\u2003\u00b5g to 800\u2003\u00b5g in healthy Japanese adults. Adverse events were mild or moderate.<\/jats:p>","DOI":"10.1111\/j.1753-5174.2008.00007.x","type":"journal-article","created":{"date-parts":[[2008,6,17]],"date-time":"2008-06-17T14:05:38Z","timestamp":1213711538000},"page":"43-49","source":"Crossref","is-referenced-by-count":2,"title":["Dose Proportionality of Fentanyl Buccal Tablet in Healthy Japanese Volunteers"],"prefix":"10.1111","volume":"1","author":[{"given":"Mona","family":"Darwish","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth","family":"Tempero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John G.","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip G.","family":"Simonson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,9,2]]},"reference":[{"key":"e_1_2_6_2_2","volume-title":"Fentora [prescribing information","year":"2007"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.2165\/00137696-200604010-00001"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2006.05.015"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000539-199601000-00031"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1177\/0091270004271969"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026451721686"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.8.13.2011"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200645080-00006"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1177\/0091270006294129"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2006.05.016"}],"container-title":["Archives of Drug Information"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1753-5174.2008.00007.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1753-5174.2008.00007.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T01:00:27Z","timestamp":1697072427000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1753-5174.2008.00007.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,9]]},"references-count":10,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2008,9]]}},"alternative-id":["10.1111\/j.1753-5174.2008.00007.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1753-5174.2008.00007.x","archive":["Portico"],"relation":{},"ISSN":["1753-5174","1753-5174"],"issn-type":[{"value":"1753-5174","type":"print"},{"value":"1753-5174","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,9]]}}}