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

  • Vet Dermatol. 2019 Apr;30(2):91-e24. doi: 10.1111/vde.12727.
Sarah Ehling  1  2 ,  Wolfgang Bäumer  1  2 ,  Mark G Papich  1
Affiliations
  • 1. Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1052 William Moore Drive, Raleigh, NC, 27606, USA.
  • 2. Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Freie Universität Berlin, Koserstrasse 20, 14195, Berlin, Germany.
PMID: 30779257 DOI: 10.1111/vde.12727
Abstract

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.

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