{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T02:30:04Z","timestamp":1791772204441,"version":"4.3.4"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T00:00:00Z","timestamp":1697587200000},"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. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Betahistine was registered in Europe in the 1970s and approved in more than 80 countries as a first-line treatment for Meni\u00e8re's disease. It has been administered to more than 150 million patients. However, according to a Cochrane systematic review of betahistine and recent meta-analyses, there is insufficient evidence to say whether betahistine has any effect in the currently approved dosages of up to 48 mg\/d. A combination with the monoamine oxidase B (MAO-B) inhibitor, selegiline, may increase the bioavailability of betahistine to levels similar to the well-established combination of L-DOPA with carbidopa or benserazide in the treatment of Parkinson's disease. We investigated the effect of selegiline on betahistine pharmacokinetics and the safety of the combination in humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In an investigator-initiated prospective, non-randomized, single-sequence, two-period titration, open label single-center phase 1 study, 15 healthy volunteers received three single oral dosages of betahistine (24, 48, and 96 mg in this sequence with at least 2 days' washout period) without and with selegiline (5 mg\/d with a loading period of 7 days). Betahistine serum concentrations were measured over a period of 240 min at eight time points (area under the curve, AUC0-240 min). This trial is registered with EudraCT (2019-002610-39) and <jats:ext-link>ClinicalTrials.gov<\/jats:ext-link>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Findings<\/jats:title><jats:p>In all three single betahistine dosages, selegiline increased the betahistine bioavailability about 80- to 100-fold. For instance, the mean (\u00b1SD) of the area under curve for betahistine 48 mg alone was 0.64 (+\/-0.47) h<jats:sup>*<\/jats:sup>ng\/mL and for betahistine plus selegiline 53.28 (+\/-37.49) h<jats:sup>*<\/jats:sup>ng\/mL. The half-life time of around 30 min was largely unaffected, except for the 24 mg betahistine dosage. In total, 14 mild adverse events were documented.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>This phase 1 trial shows that the MAO-B inhibitor selegiline increases betahistine bioavailability by a factor of about 80 to 100. No safety concerns were detected. Whether the increased bioavailability has an impact on the preventive treatment of Meni\u00e8re's disease, acute vestibular syndrome, or post-BPPV residual dizziness has to be evaluated in placebo-controlled trials.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration<\/jats:title><jats:p><jats:ext-link>https:\/\/clinicaltrials.gov\/study\/NCT05938517?intr=betahistine%20and%20selegiline&amp;amp;rank=1<\/jats:ext-link>, identifier: NCT05938517.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2023.1271640","type":"journal-article","created":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T09:21:27Z","timestamp":1697620887000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Examination of betahistine bioavailability in combination with the monoamine oxidase B inhibitor, selegiline, in humans\u2014a non-randomized, single-sequence, two-period titration, open label single-center phase 1 study (PK-BeST)"],"prefix":"10.3389","volume":"14","author":[{"given":"Michael","family":"Strupp","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant C.","family":"Churchill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivonne","family":"Naumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Mansmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amani","family":"Al 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