{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:37:25Z","timestamp":1788352645830,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,2,19]],"date-time":"2019-02-19T00:00:00Z","timestamp":1550534400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Veterinary Dermatology"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Histamine type\u20101 (H1) receptor antagonists such as diphenhydramine are frequently used for treatment of pruritus in dogs, yet therapeutic efficacy for allergic disorders is reported to be highly variable. Dimenhydrinate is a salt of diphenhydramine and 8\u2010chlorotheophylline, and has been reported to produce superior oral absorption of diphenhydramine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Hypothesis\/Objective<\/jats:title><jats:p>To determine the pharmacokinetic and pharmacodynamic properties of diphenhydramine in dogs after intravenous (1\u00a0mg\/kg) and oral (5\u00a0mg\/kg) administration, and when given orally as dimenhydrinate at a dose of 10\u00a0mg\/kg (\u22485\u00a0mg\/kg diphenhydramine).<\/jats:p><\/jats:sec><jats:sec><jats:title>Animals<\/jats:title><jats:p>Each drug was administered to six healthy, fasted mixed\u2010breed dogs in a research facility, using a cross\u2010over design.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and materials<\/jats:title><jats:p>Blood samples were collected for pharmacokinetic analysis of diphenhydramine and chlorotheophylline at defined intervals. Pharmacodynamic response was measured by histamine\u2010mediated cutaneous wheal formation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There was great variability in the data and one dog was an extreme outlier. The mean systemic availabilities of diphenhydramine were 7.8% and 22.0% after oral administration of diphenhydramine and dimenhydrinate, respectively, whereas the mean maximum concentrations were 36 (\u00b1 20) and 124 (\u00b1 46)\u00a0ng\/<jats:styled-content style=\"fixed-case\">mL<\/jats:styled-content>. The terminal elimination half\u2010lives of diphenhydramine and dimenhydrinate were 5.0 (\u00b1 7.1) and 11.6 (\u00b1 17.7)\u00a0h, respectively. Plasma diphenhydramine concentrations did not correlate with the percentage reduction in histamine\u2010induced wheal formation. Theophylline reached plasma concentrations considered to be therapeutic for dogs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Oral absorption of diphenhydramine was approximately three times greater with a longer half\u2010life when it was administered as the combination product dimenhydrinate.<\/jats:p><\/jats:sec>","DOI":"10.1111\/vde.12727","type":"journal-article","created":{"date-parts":[[2019,2,19]],"date-time":"2019-02-19T08:26:34Z","timestamp":1550564794000},"page":"91","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Diphenhydramine pharmacokinetics after oral and intravenous administration of diphenhydramine and oral administration of dimenhydrinate to healthy dogs, and pharmacodynamic effect on histamine\u2010induced wheal formation: a pilot study"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5114-9946","authenticated-orcid":false,"given":"Sarah","family":"Ehling","sequence":"first","affiliation":[{"name":"Department of Molecular Biomedical Sciences College of Veterinary Medicine North Carolina State University 1052 William Moore Drive Raleigh NC 27606 USA"},{"name":"Institute of Pharmacology and Toxicology Faculty of Veterinary Medicine Freie Universit\u00e4t Berlin Koserstrasse 20 14195 Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"B\u00e4umer","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedical Sciences College of Veterinary Medicine North Carolina State University 1052 William Moore Drive Raleigh NC 27606 USA"},{"name":"Institute of Pharmacology and Toxicology Faculty of Veterinary Medicine Freie Universit\u00e4t Berlin Koserstrasse 20 14195 Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark G.","family":"Papich","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedical Sciences College of Veterinary Medicine North Carolina State University 1052 William Moore Drive Raleigh NC 27606 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,19]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706440"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3164.2012.01088.x"},{"key":"e_1_2_6_4_1","first-page":"210","volume":"11","author":"Olivry T","year":"2015","journal-title":"Treatment of canine atopic dermatitis: 2015 updated guidelines from the International Committee on Allergic Diseases of Animals (ICADA)"},{"key":"e_1_2_6_5_1","first-page":"411","volume-title":"Veterinary Pharmacology and Therapeutics","author":"Adams HR","year":"2009"},{"key":"e_1_2_6_6_1","first-page":"88","article-title":"Antihistamines in the management of canine atopic dermatitis: a retrospective study of 171 dogs (1992\u20101998)","volume":"3","author":"Zur G","year":"2002","journal-title":"Vet Ther"},{"key":"e_1_2_6_7_1","unstructured":"USA Food and Drug Administration.Diphenhydramine. 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