{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T23:49:35Z","timestamp":1785455375109,"version":"3.56.0"},"reference-count":22,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2011,12,15]],"date-time":"2011-12-15T00:00:00Z","timestamp":1323907200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cephalalgia"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:p>Background: Dihydroergotamine (DHE), a proven migraine treatment, currently has product labeling warning against concomitant use of CYP3A4 inhibitors because of potential drug interactions. However, no reported studies of such interactions with DHE administered by any route are available.<\/jats:p>\n                  <jats:p>Methods: The pharmacokinetics (PK) of MAP0004, an investigative inhaled DHE formulation, were assessed in human subjects with and without CYP3A4 inhibition by ketoconazole to evaluate the potential for drug interaction, elevation of DHE levels, and increased adverse effects.<\/jats:p>\n                  <jats:p>\n                    Results: After MAP0004 alone vs. MAP0004 plus ketoconazole, the DHE maximum concentrations (C\n                    <jats:sub>max<\/jats:sub>\n                    ) and area-under-the-curve (AUC\n                    <jats:sub>0\u201348<\/jats:sub>\n                    and AUC\n                    <jats:sub>0\u2013\u221e<\/jats:sub>\n                    ) were not statistically significantly different nor was the C\n                    <jats:sub>max<\/jats:sub>\n                    of the primary metabolite, 8\u2019-OH-DHE. A difference in 8\u2019-OH-DHE AUCs was observed between MAP0004 with and without ketoconazole; however, the concentrations were very low. MAP0004 was well tolerated after both treatments.\n                  <\/jats:p>\n                  <jats:p>Conclusions: This study demonstrated that CYP3A4 inhibition had little to no effect on DHE PK after MAP0004 administration, apparently because of its high systemic and low gastrointestinal bioavailability. CYP3A4 inhibition slowed elimination of the metabolite 8\u2019-OH-DHE, but concentrations were too low to be pharmacologically relevant.<\/jats:p>","DOI":"10.1177\/0333102411432299","type":"journal-article","created":{"date-parts":[[2011,12,16]],"date-time":"2011-12-16T00:14:20Z","timestamp":1323994460000},"page":"150-158","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":20,"title":["Lack of drug interaction between the migraine drug MAP0004 (orally inhaled dihydroergotamine) and a CYP3A4 inhibitor in humans"],"prefix":"10.1177","volume":"32","author":[{"given":"D","family":"Kellerman","sequence":"first","affiliation":[{"name":"MAP Pharmaceuticals, Inc., USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Kori","sequence":"additional","affiliation":[{"name":"MAP Pharmaceuticals, Inc., USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Forst","sequence":"additional","affiliation":[{"name":"MAP Pharmaceuticals, Inc., USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Chang","sequence":"additional","affiliation":[{"name":"MAP Pharmaceuticals, Inc., USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Febbraro","sequence":"additional","affiliation":[{"name":"Simbec Research Limited, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"WuTann","sequence":"additional","affiliation":[{"name":"Simbec Research Limited, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Thomas","sequence":"additional","affiliation":[{"name":"Simbec Research Limited, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Taylor","sequence":"additional","affiliation":[{"name":"Welsh School of Pharmacy, Cardiff University, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DW","family":"Dodick","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic in Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2011,12,15]]},"reference":[{"key":"bibr1-0333102411432299","doi-asserted-by":"publisher","DOI":"10.1046\/j.1526-4610.2003.03034.x"},{"key":"bibr2-0333102411432299","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-2982.2008.01578.x"},{"key":"bibr3-0333102411432299","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1982.tb01866.x"},{"key":"bibr4-0333102411432299","doi-asserted-by":"publisher","DOI":"10.1007\/BF00542142"},{"key":"bibr5-0333102411432299","doi-asserted-by":"publisher","DOI":"10.3109\/00498258909043180"},{"key":"bibr6-0333102411432299","doi-asserted-by":"publisher","DOI":"10.1007\/BF03188756"},{"key":"bibr7-0333102411432299","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-8206.1991.tb00700.x"},{"key":"bibr8-0333102411432299","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-109-3-249_1"},{"key":"bibr9-0333102411432299","first-page":"205","volume":"7","author":"Franco A","year":"1978","journal-title":"Nouv Presse Med"},{"key":"bibr10-0333102411432299","unstructured":"D.H.E. 45 (dihydroergotamine mesylate) injection (package insert). Valeant Pharmaceuticals, Aliso Viejo, CA, 2009."},{"key":"bibr11-0333102411432299","unstructured":"Migranal\n                      \u00ae\n                      (dihydroergotamine mesylate) nasal spray (package insert). Valeant Pharmaceuticals, Aliso Viejo, CA, 2007."},{"key":"bibr12-0333102411432299","first-page":"687","volume":"3","author":"Cook RO","year":"2006","journal-title":"Respir Drug Deliv"},{"key":"bibr13-0333102411432299","first-page":"1","volume":"51","author":"Berenberg E","year":"2011","journal-title":"Headache"},{"key":"bibr14-0333102411432299","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2009.01510.x"},{"key":"bibr15-0333102411432299","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2007.01006.x"},{"key":"bibr16-0333102411432299","unstructured":"Kellerman D, Kori S, Forst A, et al. The major metabolite of dihydroergotamine (DHE) after oral inhalation and IV administration does not significantly contribute to the pharmacologic activity. Presented at the 63rd Annual Meeting of the American Association of Neurology, April 2011."},{"key":"bibr17-0333102411432299","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/S0090-9556(25)08600-3","volume":"18","author":"Pichard L","year":"1990","journal-title":"Drug Metab Dispos"},{"key":"bibr18-0333102411432299","unstructured":"FDA Center for Drug Evaluation and Research (CDER). Guidance for industry: in\u00a0vivo drug metabolism\/drug interaction studies \u2013 study design, data analysis, and recommendations for dosing and labeling. November 1999."},{"key":"bibr19-0333102411432299","unstructured":"Atiee G, Lasseter K, Baughman S, et al. Absence of pharmacokinetic interaction between intravenous peramivir and oral oseltamivir or rimantadine in humans.\n                      J Clin Pharmacol.\n                      Epub ahead of print 29 September 2011."},{"key":"bibr20-0333102411432299","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.161893"},{"issue":"1","key":"bibr21-0333102411432299","first-page":"S33","volume":"37","author":"Lipton RB","year":"1997","journal-title":"Headache"},{"key":"bibr22-0333102411432299","doi-asserted-by":"publisher","DOI":"10.1185\/03007990802160677"}],"container-title":["Cephalalgia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0333102411432299","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0333102411432299","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0333102411432299","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:46:21Z","timestamp":1777387581000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0333102411432299"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,12,15]]},"references-count":22,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2012,1]]}},"alternative-id":["10.1177\/0333102411432299"],"URL":"https:\/\/doi.org\/10.1177\/0333102411432299","relation":{},"ISSN":["0333-1024","1468-2982"],"issn-type":[{"value":"0333-1024","type":"print"},{"value":"1468-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,12,15]]}}}