{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T11:24:56Z","timestamp":1761218696471,"version":"3.40.5"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Clomipramine (CLOMI) has shown effectiveness in treating premature ejaculation but is linked to erectile dysfunction and reduced libido. Yohimbine (YOH), by contrast, is effective in treating erectile dysfunction and may improve libido. Combining CLOMI and YOH could potentially leverage the benefits of both drugs. This study aimed to investigate the interactions between these drugs and to evaluate their safety profile.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A prospective, open\u2010labelled, single\u2010centre, pharmacokinetic (PK) drug\u2013drug interaction study was performed in 15 healthy male subjects. Single\u2010dose and steady\u2010state PK were investigated using noncompartmental analysis after mono\u2010 and combination therapy of the 2 orally applied drugs. Plasma sampling was performed at baseline, 0.5 (YOH), 1, 1.5 (YOH), 2, 3, 4, 5, 6, 8, 12 and 24\u2009h (CLOMI). Differences in the area under the curve after multiple dosing (MD) were determined using an equivalence boundary of 80\u2013125%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The geometric mean ratio of the area under the curve up to 12 h for MD CLOMI (combination <jats:italic>vs<\/jats:italic>. monotherapy) was 112% (90% confidence interval: 104\u2013120%), whereas for MD YOH this ratio was 137% (90% confidence interval: 112\u2013168%). The study drugs were safe and well tolerated as mono\u2010 and combination therapy, with no major adverse events reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A PK assessment of clomipramine and yohimbine indicated a clinically significant drug\u2013drug interaction for MD YOH in combination with CLOMI. This might be explained by competitive, CLOMI\u2010related inhibition of YOH metabolism, probably mediated by cytochrome P450 2D6. However, according to European Medicines Agency guidelines, the effect can be classified as interaction absent (&lt;1,25 fold) or minor (&gt;1.25\u2013&lt;2\u2010fold). Given the complimentary mechanisms of action and the favourable safety profiles, the findings pave the way for future efficacy studies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16274","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T07:49:41Z","timestamp":1729496981000},"page":"808-816","source":"Crossref","is-referenced-by-count":1,"title":["Single\u2010dose and steady\u2010state pharmacokinetics of clomipramine, yohimbine and clomipramine\/yohimbine combination: A clinical drug\u2013drug interaction study"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1424-843X","authenticated-orcid":false,"given":"Amelie","family":"Leutzendorff","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology Medical University of Vienna  Austria"},{"name":"Department of Medicine I Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna  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