{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T06:08:14Z","timestamp":1772777294650,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    To assess the antitussive effects of dextrorphan (DOR) relative to its parent compound, dextromethorphan (DEX) a double\u2010blind, randomized, placebo\u2010controlled crossover study was conducted in 23 healthy volunteers using citric acid cough challenge test after administering placebo, DEX, or DOR. Plasma concentrations and cough frequency were monitored over 24 h, followed by model independent analysis and pharmacokinetic\u2010pharmacodynamic (PKPD) modelling to discern the relative potency of each moiety. Model\u2010independent pairwise analysis of the area under the effect curve (AUEC\u2080\u208b\u2082\u2084\u00a0\n                    <jats:sub>h<\/jats:sub>\n                    ) showed no significant difference between DOR, DEX, and placebo's antitussive effects (\n                    <jats:italic>P<\/jats:italic>\n                    &gt; \u00a0.06), indicating the influence of considerable inter\u2010individual variability and the need for larger sample sizes. The model\u2010based analysis established DOR's relative potency at 26% compared to DEX, with maximum cough inhibition of 23% and IC50 of 0.3 ng\/mL. PKPD measures were more accurate for DEX than DOR, particularly at lower baseline cough counts. In conclusion, while DOR retains some antitussive potency, since it is substantially less potent than DEX, higher relative concentrations are required to reach the same effect. Although separate administration of metabolite on its own is considered gold standard to establish its relative potency compared to parent compound, the variability in effect may prevent clear demonstration of effects without modelling particularly when these take benefit of the perturbing the balance of parent\/metabolite ratios (e.g. via inhibition) or using the natural variational of such ratios in different individuals.\n                  <\/jats:p>","DOI":"10.1002\/jcph.70049","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T09:09:13Z","timestamp":1747386553000},"page":"1616-1625","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dextromethorphan Versus Dextrorphan: A Quantitative Comparison of Antitussive Potency Following Separate Administration of Metabolite"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6135-9610","authenticated-orcid":false,"given":"Saeed","family":"Rezaee","sequence":"first","affiliation":[{"name":"Centre for Applied Pharmacokinetic Research, University of Manchester  Manchester UK"},{"name":"School of Pharmacy, Zanjan University of Medical Sciences  Zanjan Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline E.","family":"Wright","sequence":"additional","affiliation":[{"name":"Respiratory Medicine, Centre for Clinical Science, Hull York Medical School  Hull UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alyn H.","family":"Morice","sequence":"additional","affiliation":[{"name":"Respiratory Medicine, Centre for Clinical Science, Hull York Medical School  Hull UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amin","family":"Rostami\u2010Hodjegan","sequence":"additional","affiliation":[{"name":"Centre for 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