{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T13:51:51Z","timestamp":1788616311095,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,3]],"date-time":"2024-11-03T00:00:00Z","timestamp":1730592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Zavegepant (ZAVZPRET\u2122) is a high\u2010affinity, selective, small\u2010molecule calcitonin gene\u2010related peptide receptor antagonist available for acute treatment of migraine in adults. A population pharmacokinetic analysis was performed to describe zavegepant plasma concentration\u2013time course, characterize bioavailability, and identify covariates affecting zavegepant exposure. The model was developed and validated using data from 10 phase I clinical studies, wherein zavegepant was administered intravenously, intranasally, or orally to healthy adults and patients with migraine. Plasma concentration\u2013time data were analyzed using nonlinear mixed\u2010effects modeling. A three\u2010compartment model with first\u2010order elimination from the central compartment, and sequential zero\u2010 and first\u2010order absorption best described the observed plasma concentration\u2013time course of zavegepant. Bioavailability was 5.1% and 0.65% for intranasal and oral treatment, respectively; absorption rate constants were 5.8 and 0.8\u2009h<jats:sup>\u22121<\/jats:sup>, respectively. Body weight\u2010based empirical allometric scaling was applied using standard exponents (0.75 for clearance and 1 for volume of distribution). Age (range 18\u201371\u2009years), race, ethnicity, sex, renal function, and co\u2010administration of oral contraceptives or sumatriptan did not significantly change zavegepant pharmacokinetics. Moderate hepatic impairment (Child\u2010Pugh score 7\u20139) or co\u2010administration of rifampin decreased elimination clearance of oral zavegepant by ~40%. The zavegepant population pharmacokinetic model adequately characterized zavegepant concentration\u2013time profiles, the bioavailability of intranasal and oral zavegepant, as well as the effect of intrinsic and extrinsic factors on zavegepant pharmacokinetics.<\/jats:p>","DOI":"10.1002\/psp4.13257","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T07:43:38Z","timestamp":1730706218000},"page":"179-191","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Population pharmacokinetic modeling of zavegepant, a calcitonin gene\u2010related peptide receptor antagonist, in healthy adults and patients with migraine"],"prefix":"10.1002","volume":"14","author":[{"given":"Craig M.","family":"Comisar","sequence":"first","affiliation":[{"name":"Certara Inc.  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2956-1237","authenticated-orcid":false,"given":"Jose","family":"Francis","sequence":"additional","affiliation":[{"name":"Certara Inc.  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1862-5805","authenticated-orcid":false,"given":"Jim H.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2720-2192","authenticated-orcid":false,"given":"Rajinder","family":"Bhardwaj","sequence":"additional","affiliation":[{"name":"Certara Inc.  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4593-1310","authenticated-orcid":false,"given":"Richard","family":"Bertz","sequence":"additional","affiliation":[{"name":"Biohaven Pharmaceuticals Inc.  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9481-5961","authenticated-orcid":false,"given":"Jing","family":"Liu","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  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