{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T14:33:36Z","timestamp":1774362816989,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    DW\u20101021 is a novel fixed\u2010dose combination salt formulation containing pelubiprofen 45\u00a0mg and tramadol hydrochloride 45.9\u00a0mg (equivalent to 40.3\u00a0mg tramadol free base). Two open\u2010label, phase I clinical studies were conducted in healthy Vietnamese male volunteers to characterize the pharmacokinetics of DW\u20101021. The relative bioavailability study employed a randomized, single\u2010dose, two\u2010period, two\u2010sequence crossover design (n = 14) comparing DW\u20101021 with co\u2010administration of Pelubi CR (pelubiprofen 45\u00a0mg) and Zytram CR (tramadol hydrochloride 75\u00a0mg, equivalent to 65.9\u00a0mg tramadol base) under fasting conditions. The food effect study used a fixed\u2010sequence, two\u2010period design (n = 14) to evaluate DW\u20101021 under fasting and fed (high\u2010fat, high\u2010calorie) conditions. In the relative bioavailability study, DW\u20101021 resulted in lower exposure to pelubiprofen (AUC\n                    <jats:sub>0\u2010t<\/jats:sub>\n                    GMR: 86.68%) and generally comparable exposure to trans\u2010OH\u2010pelubiprofen (AUC\n                    <jats:sub>0\u2010t<\/jats:sub>\n                    GMR: 108.74%) compared with the reference treatment. For tramadol, unadjusted comparisons showed a higher peak concentration (C\n                    <jats:sub>max<\/jats:sub>\n                    GMR: 192.17%) but lower overall exposure (AUC\n                    <jats:sub>0\u2010t<\/jats:sub>\n                    GMR: 79.30%). After dose normalization, tramadol exposure per unit dose was higher (AUC\n                    <jats:sub>0\u2010t<\/jats:sub>\n                    \/Dose GMR: 129.58%). In the food effect study, fasting conditions were associated with higher C\n                    <jats:sub>max<\/jats:sub>\n                    and AUC\n                    <jats:sub>0\u2010t<\/jats:sub>\n                    of pelubiprofen (GMRs: 109.92% and 140.48%, respectively). Food increased tramadol C\n                    <jats:sub>max<\/jats:sub>\n                    , while AUC\n                    <jats:sub>0\u2010t<\/jats:sub>\n                    remained largely comparable between conditions. All adverse events were mild to moderate, and no serious adverse events were reported. In conclusion, DW\u20101021 exhibited analyte\u2010dependent pharmacokinetic differences relative to the reference treatment. Food intake primarily reduced pelubiprofen exposure, while tramadol AUC\n                    <jats:sub>0\u2010t<\/jats:sub>\n                    was minimally affected, with a modest increase in C\n                    <jats:sub>max<\/jats:sub>\n                    under fed conditions.\n                  <\/jats:p>","DOI":"10.1002\/cpdd.70050","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T05:29:05Z","timestamp":1773379745000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetic Evaluation of a Fixed\u2010Dose Combination of Pelubiprofen and Tramadol: A Randomized Crossover Relative Bioavailability Trial and a Fixed\u2010Sequence Food\u2010Effect Study in Healthy Volunteers"],"prefix":"10.1002","volume":"15","author":[{"given":"Bui Thi","family":"Tham","sequence":"first","affiliation":[{"name":"Centre for Clinical Trial and Bioequivalence Study, Faculty of Pharmacy Hai Phong University of Medicine and Pharmacy  Hai Phong Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tran Thi","family":"Ngan","sequence":"additional","affiliation":[{"name":"Centre for Clinical Trial and Bioequivalence Study, Faculty of Pharmacy Hai Phong University of Medicine and Pharmacy  Hai Phong Vietnam"},{"name":"Department of Pharmacy Hai Phong International Hospital  Hai Phong Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tran","family":"Van Anh","sequence":"additional","affiliation":[{"name":"Centre for Clinical Trial and Bioequivalence Study, Faculty of Pharmacy Hai Phong University of Medicine and Pharmacy  Hai Phong Vietnam"},{"name":"Department of Pharmacy Hai Phong International Hospital  Hai Phong Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim Dong","family":"Chool","sequence":"additional","affiliation":[{"name":"Office of the CEO Aimedisurvey Company  Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee Ah","family":"Ram","sequence":"additional","affiliation":[{"name":"R&amp;D Division Daewon Pharm. Co., Ltd.  Seongdong\u2010gu Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Park Sang","family":"Wook","sequence":"additional","affiliation":[{"name":"R&amp;D Division Daewon Pharm. Co., Ltd.  Seongdong\u2010gu Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee Soo","family":"Bok","sequence":"additional","affiliation":[{"name":"R&amp;D Division Daewon Pharm. Co., Ltd.  Seongdong\u2010gu Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oh Dong","family":"Ho","sequence":"additional","affiliation":[{"name":"R&amp;D Division Daewon Pharm. Co., Ltd.  Seongdong\u2010gu Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nguyen","family":"Van Khai","sequence":"additional","affiliation":[{"name":"Faculty of Public Health Hai Phong University of Medicine and Pharmacy  Hai Phong Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nguyen Thi Thu","family":"Phuong","sequence":"additional","affiliation":[{"name":"Centre for Clinical Trial and Bioequivalence Study, Faculty of Pharmacy Hai Phong University of Medicine and Pharmacy  Hai Phong Vietnam"},{"name":"Department of Pharmacy Hai Phong International Hospital  Hai Phong Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001939"},{"key":"e_1_2_8_3_1","unstructured":"Committee for Medicinal Products for Human Use (CHMP).Guideline on the clinical development of medicinal products intended for the treatment of pain. 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Department of Health and Human Services, United States; Food and Drug Administration; Center for Drug Evaluation and Research (U.S.)","year":"2022"},{"key":"e_1_2_8_29_1","unstructured":"DailyMed. Tramadol hydrochloride ER\u2014tramadol hydrochloride tablet extended release. U.S. National Library of Medicine. 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