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The multidimensional pharmacodynamic profiles of ibuprofen 400\u00a0mg\/paracetamol 1000\u00a0mg, ibuprofen 400\u00a0mg\/paracetamol 1000\u00a0mg\/codeine 60\u00a0mg, and paracetamol 1000\u00a0mg\/codeine 60\u00a0mg and placebo were compared.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A randomized, double-blind, placebo-controlled, parallel-group, single-centre, outpatient, and single-dose study used 200 patients of both sexes and homogenous ethnicity after third molar surgery (mean age 24\u00a0years, range 19\u201330\u00a0years). Primary outcome was sum pain intensity over 6\u00a0h (SPI). Secondary outcomes were time to analgesic onset, duration of analgesia, time to rescue drug intake, number of patients taking rescue drug, sum pain intensity difference (SPID), maximum pain intensity difference, time to maximum pain intensity difference, number needed to treat, prevent remedication and harm values, adverse effects, and patient-reported outcome measure (PROM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Analgesia following ibuprofen and paracetamol combination with or without codeine was comparable. Both were better than paracetamol combined with codeine. Secondary variables supported this finding. Post hoc analysis of SPI and SPID revealed a sex\/drug interaction trend in the codeine-containing groups where females experienced less analgesia. PROM showed a significant sex\/drug interaction in the paracetamol and codeine group, but not in the other codeine-containing group. Especially females reported known and mild side effects in the codeine-containing groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Codeine added to ibuprofen\/paracetamol does not seem to add analgesia in a sex-mixed study population. Sex may be a confounding factor when testing weak opioid analgesics such as codeine. PROM seems to be more sensitive than traditional outcome measures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov June 2009 NCT00921700.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00228-023-03525-0","type":"journal-article","created":{"date-parts":[[2023,6,23]],"date-time":"2023-06-23T13:33:14Z","timestamp":1687527194000},"page":"1131-1141","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Analgesic effect of oral paracetamol 1000\u00a0mg\/ibuprofen 400\u00a0mg, paracetamol 1000\u00a0mg\/codeine 60\u00a0mg, paracetamol 1000\u00a0mg\/ibuprofen 400\u00a0mg\/codeine 60\u00a0mg, or placebo on acute postoperative pain: a single-dose, randomized, and double-blind study"],"prefix":"10.1007","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3169-3287","authenticated-orcid":false,"given":"Gaute","family":"Lyngstad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5193-7827","authenticated-orcid":false,"given":"Per","family":"Skjelbred","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3174-1656","authenticated-orcid":false,"given":"David Michael","family":"Swanson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1863-2738","authenticated-orcid":false,"given":"Lasse Ansgar","family":"Skoglund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,6,22]]},"reference":[{"key":"3525_CR1","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1002\/cpt1976202241","volume":"20","author":"SA Cooper","year":"1976","unstructured":"Cooper SA, Beaver WT (1976) A model to evaluate mild analgesics in oral surgery outpatients. 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The trial was registered June 2009 (ClinicalTrial.gov NCT00921700).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Patients provided written informed consent prior to any screening and study-related procedures and consented to publication of the results.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Patient consent"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}