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This study aimed to determine whether isotretinoin administration changes CYP2D6 and CYP3A activities in patients with severe acne.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty\u2010three patients (22 females and 11 males, 23.5\u2009\u00b1\u20096.0\u00a0years old) expected to receive isotretinoin treatment completed the study. All participants were genotyped for CYP2D6 and CYP3A5. Participants received dextromethorphan (DM) 30\u2009mg orally as a dual\u2010probe substrate of CYP2D6 and CYP3A activity at two study timepoints: pre\u2010isotretinoin treatment and with isotretinoin for at least 1\u00a0week. The concentrations of isotretinoin, DM and their metabolites were measured in 2\u2010h postdose plasma samples and in cumulative 0\u20104\u2010h urine collections using liquid chromatography\u2010mass spectrometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In CYP2D6 extensive metabolizers, the urinary dextrorphan (DX)\/DM metabolic ratio (MR) (CYP2D6 activity marker) was numerically, but not significantly, lower with isotretinoin administration compared to pre\u2010isotretinoin (geometric mean ratio [GMR] [90% confidence interval (CI)] 0.78 [0.55, 1.11]). The urinary 3\u2010hydroxymorphinan (3HM)\/DX MR (CYP3A activity marker) was increased (GMR 1.18 [1.03, 1.35]) and the urinary DX\u2010O\u2010glucuronide\/DX MR (proposed UGT2B marker) was increased (GMR 1.22 [1.06, 1.39]) with isotretinoin administration compared to pre\u2010isotretinoin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Administration of isotretinoin did not significantly reduce CYP2D6 activity in extensive metabolizers, suggesting that the predicted downregulation of CYP2D6 based on in vitro data does not translate into humans. We observed a modest increase in CYP3A activity (predominantly CYP3A4) with isotretinoin treatment. The data also suggest that DX glucuronidation is increased following isotretinoin administration.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15938","type":"journal-article","created":{"date-parts":[[2023,10,21]],"date-time":"2023-10-21T05:59:24Z","timestamp":1697867964000},"page":"759-768","source":"Crossref","is-referenced-by-count":0,"title":["Effect of isotretinoin on CYP2D6 and CYP3A activity in patients with severe acne"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8768-673X","authenticated-orcid":false,"given":"Yuqian","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics University of Washington, School of Pharmacy  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"Jay C.","family":"Vary","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Dermatology University of Washington, School of Medicine  Seattle Washington 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