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Diphenhydramine pharmacokinetics after oral and intravenous administration of diphenhydramine and oral administration of dimenhydrinate to healthy dogs, and pharmacodynamic effect on histamine‐induced wheal formation: a pilot study
Author(s) -
Ehling Sarah,
Bäumer Wolfgang,
Papich Mark G.
Publication year - 2019
Publication title -
veterinary dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.744
H-Index - 60
eISSN - 1365-3164
pISSN - 0959-4493
DOI - 10.1111/vde.12727
Subject(s) - diphenhydramine , medicine , pharmacokinetics , pharmacodynamics , anesthesia , oral administration , histamine , pharmacology
Background Histamine type‐1 (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‐chlorotheophylline, and has been reported to produce superior oral absorption of diphenhydramine. Hypothesis/Objective To determine the pharmacokinetic and pharmacodynamic properties of diphenhydramine in dogs after intravenous (1 mg/kg) and oral (5 mg/kg) administration, and when given orally as dimenhydrinate at a dose of 10 mg/kg (≈5 mg/kg diphenhydramine). Animals Each drug was administered to six healthy, fasted mixed‐breed dogs in a research facility, using a cross‐over design. Methods and materials Blood samples were collected for pharmacokinetic analysis of diphenhydramine and chlorotheophylline at defined intervals. Pharmacodynamic response was measured by histamine‐mediated cutaneous wheal formation. Results 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 (± 20) and 124 (± 46) ng/ mL . The terminal elimination half‐lives of diphenhydramine and dimenhydrinate were 5.0 (± 7.1) and 11.6 (± 17.7) h, respectively. Plasma diphenhydramine concentrations did not correlate with the percentage reduction in histamine‐induced wheal formation. Theophylline reached plasma concentrations considered to be therapeutic for dogs. Conclusion Oral absorption of diphenhydramine was approximately three times greater with a longer half‐life when it was administered as the combination product dimenhydrinate.