{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:55:28Z","timestamp":1790751328074,"version":"4.1.0"},"reference-count":13,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pain Res."],"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Paracetamol is widely used for management of fever\/pain. With increasing emphasis on rapid symptom relief, this study compared the response following a single 650\u2005mg oral dose of four commercially available tablets in acute febrile and febrile-pain conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter, open-label trial (CTRI\/2025\/12\/098995) included adults (18\u201360 years) with oral temperature \u226538\u2005\u00b0C (with\/without pain) and symptom onset within \u226472\u2005h. Consenting participants were randomized (1:1:1:1) to receive a single dose of the test fast release test paracetamol (A) and conventional paracetamol (B, C, D) drug. Oral body temperature(digital thermometer) and pain (numerical rating scale (NRS) were assessed at predefined intervals till 90\u2009\u00b1\u20092\u2005min. Outcomes included magnitude and onset of antipyretic and analgesic effects, adverse events (AEs), and patient satisfaction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 220 febrile participants (55% women; mean temperature 38.51\u2005\u00b0C), 169 reported pain (mean NRS score 7.31). At 90\u2009\u00b1\u20092\u2005min, fast release paracetamol demonstrated significantly greater reduction in temperature (1.54\u2005\u00b0C), along with the fastest rate of decline (1.03\u2005\u00b0C\/hr), and the shortest restricted mean time to defervescence (84.27\u2005min), resulting in majority of participants (60.0%) experiencing defervescence (temperature \u226437\u2005\u00b0C). Pain reduction was also significantly greater with fast release test paracetamol (5.2 units; 3.4 units\/hr), with onset of analgesia (\u226530% reduction in NRS score) after a comparatively shorter median time (30\u2005min; conventional, 60\u201390\u2005min). By 90\u2009\u00b1\u20092\u2005min, pain resolved (NRS score\u2009=\u20090) in 23.2% (A), 22.5% (B), 11.9% (C), and 6.8% (D) participants, with restricted mean times to resolution being 90.00, 89.25, 89.29, and 90.00\u2005min, respectively. Overall, 82.2% participants reported treatment satisfaction, with likelihood highest for fast-release test paracetamol (A). Four participants reported unrelated, mild\/moderate AEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>All evaluated paracetamol 650\u2005mg formulations demonstrated antipyretic and analgesic activity within 90\u2005min, while the fast-release formulation showed earlier and, for several assessed outcomes, greater reductions in temperature and pain. These findings may support consideration of formulation choice when rapid early symptomatic relief is desired.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>CTRI\/2025\/12\/098995.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpain.2026.1965374","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:00:45Z","timestamp":1790748045000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative evaluation of the antipyretic and analgesic efficacy and safety of a fast-release paracetamol 650\u2005mg formulation vs. conventional paracetamol formulations in adults with acute febrile or febrile-pain conditions: a multicenter randomized controlled trial"],"prefix":"10.3389","volume":"7","author":[{"given":"Susobhan","family":"Mondal","sequence":"first","affiliation":[{"name":"Apollo Clinic","place":["Salt Lake, Kolkata, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. K. Ashik","family":"Ikbal","sequence":"additional","affiliation":[{"name":"Olivia Nursing Home","place":["Dum Dum, Kolkata, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumit","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Agrawal Hospital","place":["Pune, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amar","family":"Raykantiwar","sequence":"additional","affiliation":[{"name":"Atharva Diabetes and Weight Loss Center","place":["Pune, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avirath","family":"Acchammachary","sequence":"additional","affiliation":[{"name":"Silver Birch Multispecialty Hospital","place":["Pune, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhas","family":"Kalashetti","sequence":"additional","affiliation":[{"name":"Shree Samarth Hospital","place":["Pune, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. R.","family":"Shivaprasad","sequence":"additional","affiliation":[{"name":"Dooravani Diagnostics and Multispecialty Clinic","place":["Bangalore, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok","family":"V B","sequence":"additional","affiliation":[{"name":"Dr. Ashok's Clinic","place":["Bangalore, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukulesh","family":"Gupta","sequence":"additional","affiliation":[{"name":"Udyan Healthcare Pvt Ltd.","place":["Lucknow, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikas","family":"Verma","sequence":"additional","affiliation":[{"name":"Vardhman Hospital","place":["Lucknow, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monjori","family":"Mitra","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Institute of Child Health","place":["Kolkata, West Bengal, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amitrajit","family":"Pal","sequence":"additional","affiliation":[{"name":"Alkem Laboratories Ltd.","place":["Mumbai, Maharashtra, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dattatray","family":"Pawar","sequence":"additional","affiliation":[{"name":"Alkem Laboratories Ltd.","place":["Mumbai, Maharashtra, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhilesh","family":"Sharma","sequence":"additional","affiliation":[{"name":"Alkem Laboratories Ltd.","place":["Mumbai, Maharashtra, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1080\/15563650.2021.1928163","article-title":"Population pharmacokinetics of immediate-release and modified-release paracetamol and its Major metabolites in a supratherapeutic dosing study","volume":"60","author":"Li","year":"2022","journal-title":"Clin Toxicol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1002\/cpdd.469","article-title":"Bioequivalence evaluation of two oral formulations of Acetaminophen in healthy subjects: results from a randomized, single-blind, crossover study","volume":"8","author":"Garc\u00eda Aguirre","year":"2019","journal-title":"Clin Pharmacol Drug Dev"},{"key":"B3","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1002\/jps.20477","article-title":"Biowaiver monographs for immediate release solid oral dosage forms: acetaminophen (paracetamol)","volume":"95","author":"Kalantzi","year":"2006","journal-title":"J Pharm Sci"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e029728","DOI":"10.1136\/bmjopen-2019-029728","article-title":"Efficacy and safety of modified-release paracetamol for acute and chronic pain: a systematic review protocol","volume":"9","author":"Koletic","year":"2019","journal-title":"BMJ Open"},{"key":"B5","doi-asserted-by":"publisher","first-page":"25","DOI":"10.4103\/2229-3485.124567","article-title":"Randomized comparative trial of efficacy of paracetamol, ibuprofen and paracetamol-ibuprofen combination for treatment of febrile children","volume":"5","author":"Vyas","year":"2014","journal-title":"Perspect Clin Res"},{"key":"B6","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.clinthera.2006.02.004","article-title":"Multicenter, randomized, double-blind, active-controlled, parallel-group trial of the long-term (6\u201312 months) safety of Acetaminophen in adult patients with osteoarthritis","volume":"28","author":"Temple","year":"2006","journal-title":"Clin Ther"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1016\/j.clinthera.2013.07.422","article-title":"Efficacy and speed of onset of pain relief of fast-dissolving paracetamol on postsurgical dental pain: two randomized, single-dose, double-blind, placebo-controlled clinical studies","volume":"35","author":"Yue","year":"2013","journal-title":"Clin Ther"},{"key":"B8","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1080\/03007995.2023.2294946","article-title":"Analgesic onset and efficacy of a fast-acting formulation of Acetaminophen in a postoperative dental impaction pain model","volume":"40","author":"Myers","year":"2024","journal-title":"Curr Med Res Opin"},{"key":"B9","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1002\/ejp.536","article-title":"Validating speed of onset as a key component of good analgesic response in acute pain","volume":"19","author":"Moore","year":"2015","journal-title":"Eur J Pain"},{"key":"B10","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.pain.2013.08.013","article-title":"Faster, higher, stronger? Evidence for formulation and efficacy for ibuprofen in acute pain","volume":"155","author":"Moore","year":"2014","journal-title":"Pain"},{"key":"B11","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1111\/bcp.12628","article-title":"Effects of food on pharmacokinetics of immediate release oral formulations of aspirin, dipyrone, paracetamol and NSAIDs \u2013 a systematic review","volume":"80","author":"Moore","year":"2015","journal-title":"Br J Clin Pharmacol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1080\/03007995.2024.2331159","article-title":"Clinical validation of a fast-acting Acetaminophen: a randomized, active and placebo controlled dental pain study","volume":"40","author":"Myers","year":"2024","journal-title":"Curr Med Res Opin"},{"key":"B13","doi-asserted-by":"publisher","first-page":"324","DOI":"10.5694\/mja2.50992","article-title":"The efficacy and safety of paracetamol for pain relief: an overview of systematic reviews","volume":"214","author":"Abdel Shaheed","year":"2021","journal-title":"Med J Aust"}],"container-title":["Frontiers in Pain Research"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpain.2026.1965374\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:00:46Z","timestamp":1790748046000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpain.2026.1965374\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":13,"alternative-id":["10.3389\/fpain.2026.1965374"],"URL":"https:\/\/doi.org\/10.3389\/fpain.2026.1965374","relation":{},"ISSN":["2673-561X"],"issn-type":[{"value":"2673-561X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]},"article-number":"1965374"}}