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The effects of moderate hepatic impairment (8 participants with Child\u2010Pugh score 7\u20139 points) on the pharmacokinetics of a single 10\u2010mg intranasal dose of zavegepant versus eight matched participants with normal hepatic function were evaluated in a phase I study. Pharmacokinetic sampling determined total and unbound plasma zavegepant concentrations. Moderate hepatic impairment increased the exposure of total zavegepant (~2\u2010fold increase in AUC<jats:sub>0\u2013inf<\/jats:sub> and 16% increase in C<jats:sub>max<\/jats:sub>) versus normal hepatic function, which is not considered clinically meaningful. The geometric least squares mean ratios (moderate impairment\/normal) of plasma zavegepant AUC<jats:sub>0\u2212inf<\/jats:sub> and C<jats:sub>max<\/jats:sub> were 193% (90% confidence interval [CI]: 112, 333; <jats:italic>p<\/jats:italic>\u2009=\u20090.051) and 116% (90% CI: 69, 195; <jats:italic>p<\/jats:italic>\u2009=\u20090.630), respectively. The geometric mean fraction unbound of zavegepant was similar for participants with moderate hepatic impairment (0.13; coefficient of variation [CV] 13.71%) versus those with normal hepatic function (0.11; CV 21.43%). Similar exposure findings were observed with unbound zavegepant versus normal hepatic function (~2.3\u2010fold increase in AUC<jats:sub>0\u2212inf<\/jats:sub> and 39% increase in C<jats:sub>max<\/jats:sub>). One treatment\u2010emergent adverse event (mild, treatment\u2010related headache) was reported in a participant with normal hepatic function. No dosage adjustment of intranasal zavegepant is required in adults with mild or moderate hepatic impairment.<\/jats:p>","DOI":"10.1111\/cts.13813","type":"journal-article","created":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T04:40:01Z","timestamp":1721191201000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Reduced hepatic impairment study to evaluate pharmacokinetics and safety of zavegepant and to inform dosing recommendation for hepatic impairment"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2720-2192","authenticated-orcid":false,"given":"Rajinder","family":"Bhardwaj","sequence":"first","affiliation":[{"name":"Certara USA  Princeton New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0450-5702","authenticated-orcid":false,"given":"Mary K.","family":"Donohue","sequence":"additional","affiliation":[{"name":"Biohaven Pharmaceuticals, Inc.  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