Pharmacokinetics of diphenhydramine following single‐dose intravenous and oral administration in non‐fasted adult horses

Abstract

Atopic dermatitis and recurrent urticaria are associated with type I IgE-mediated hypersensitivity in humans (Kaplan & Greaves, 2009;Leung, 1999), with evidence to support a similar relationship in horses (Equus caballus) (Rüfenacht et al., 2005;Stepnik et al., 2012).In horses, urticaria is the result of mast cell and basophil degranulation in the skin releasing histamine and other inflammatory mediators causing focal vasculitis (Hinden et al., 2012; Rüfenacht et al., 2005). One method of controlling clinical signs associated with these disorders is via corticosteroid or antihistamine administration.Corticosteroids, particularly dexamethasone and prednisolone, have demonstrated efficacy for controlling inflammation associated with urticaria in horses (Scott and Miller, 2011). However, they are not without risk of severe side effects including laminitis (Bailey, 2010) and immune suppression (Leclere, 2017).Antihistamine receptor antagonists target either H1 or H2 histamine receptors, with the latter primarily aimed at reducing gastric acid production (Furr & Murray, 1989). H1 antagonists interact with histamine receptors located on cells within various tissues (vascular endothelium, bronchial smooth muscle, and peripheral nerve endings) to stop histamine binding and therefore prevent histamine's pro-inflammatory effects (Leurs et al., 2002) that lead to clinical signs. While various H1 antagonists are commonly used in horses, including hydroxyzine,

Equine allergic skin diseases: Clinical consensus guidelines of the World Association for Veterinary Dermatology

“…Common choices of antihistamines are hydroxyzine, chlorpheniramine, cetirizine and diphenhydramine 293–296 . Of interest, a recently published study reported on the poor oral bioavailability of oral diphenhydramine in horse highlighting the need for injectable administration 312 . Pentoxifylline and essential fatty acids may be tried for chronic cases 296…”

“…[293][294][295][296] Of interest, a recently published study reported on the poor oral bioavailability of oral diphenhydramine in horse highlighting the need for injectable administration. 312 Pentoxifylline and essential fatty acids may be tried for chronic cases. 296 Currently, there is no published controlled study to evaluate the efficacy of one choice over the other as far as treatment options.…”

Combination of Different Antihistamines to Treat Urticaria and Its Effects on Serum Total Immunoglobulin E Level in Patients

“…However, symptomatic treatment of chronic urticaria with antihistamines can lead to relapse after discontinuation. Second-generation non-sedating H1 receptor antagonists are the preferred treatment for chronic urticaria, which is recognized at home and abroad, and the treatment methods include single-drug treatment and combined drug treatment with non-sedating H1 receptor antagonists [6]. Under normal conditions, IgE levels in serum samples are very low and relatively stable.…”