The pharmacokinetics of DPH after the administration of a single intravenous or intramuscular dose in healthy dogs

Abstract

The objective of this study was to determine the pharmacokinetics of diphenhydramine (DPH) in healthy dogs following a single i.v. or i.m. dose. Dogs were randomly allocated in two treatment groups and received DPH at 1 mg/kg, i.v., or 2 mg/kg, i.m. Blood samples were collected serially over 24 h. Plasma concentrations of DPH were determined by high-performance liquid chromatography, and noncompartmental pharmacokinetic analysis was performed with the commercially available software. Cardio-respiratory parameters, rectal temperature and effects on behaviour, such as sedation or excitement, were recorded. Diphenhydramine Clarea , Vdarea and T1/2 were 20.7 ± 2.9 mL/kg/min, 7.6 ± 0.7 L/kg and 4.2 ± 0.5 h for the i.v. route, respectively, and Clarea /F, Vdarea /F and T1/2 20.8 ± 2.7 mL/kg/min, 12.3 ± 1.2 L/kg and 6.8 ± 0.7 h for the i.m. route, respectively. Bioavailability was 88% after i.m. administration. No significant differences were found in physiological parameters between groups or within dogs of the same group, and values remained within normal limits. No adverse effects or changes in mental status were observed after the administration of DPH. Both routes of administration resulted in DPH plasma concentrations which exceeded levels considered therapeutic in humans.

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

“…A novel aspect of our study is the inclusion of an oral formulation of diphenhydramine, allowing for pharmacokinetic evaluation of a different route of administration. Intramuscular administration has been evaluated in dogs (Sanchez et al, 2015) but has not been investigated in horses despite the use of this route in this species.…”

“…Antihistamine binding can also be non‐specific leading to other potentially detrimental side effects (Kubo et al, 1987). While some of the side effects of diphenhydramine have been studied in dogs (Sanchez et al, 2015, 2017), these effects have yet to be investigated in horses. While our study did not focus on evaluation of adverse effects of diphenhydramine, two horses experienced excitability and hyperesthesia following IV administration.…”

“…Antihistamine binding can also be non-specific leading to other potentially detrimental side effects (Kubo et al, 1987). While some of the side effects of diphenhydramine have been studied in dogs (Sanchez et al, 2015(Sanchez et al, , 2017, A limitation of this study was its small sample size; however, the number of animals used still produced informative pharmacokinetic results. Furthermore, evaluation of metabolites was not investigated to assess for first-pass metabolism effects following oral administration that may impact plasma diphenhydramine concentrations.…”

Comparative study of the effects of antitussive drugs in a canine acute cough model

“…The Cmax of maropitant alone administered subcutaneously at 1 mg/kg was 92.0 ± 33.8 ng/mL (Benchaoui et al., 2007 ), whereas the Cmax of maropitant administered intramuscularly with morphine was 1507.6 ± 499.6 ng/mL and with both dexmedetomidine and morphine was 1269.7 ± 668.0 ng/mL (Karna et al., 2019 ). Danpron, which primarily contains diphenhydramine, reaches a Cmax in 0.7 h with a T1/2 of 6.8 ± 0.7 h following intramuscular administration (Sanchez et al., 2016 ). In the composition of Danpron, methylephedrine also has antitussive properties, but there are no pharmacokinetics data for intramuscular administration in dogs.…”

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

“…Diphenhydramine was given i.v. at a dose of 1 mg/kg (DiphenhydrAMINE ® , WEST‐WARD; Eatontown, NJ, USA) and p.o. at 5 mg/kg (Banophen ® , MAJOR Pharmaceuticals; Livonia, MI, USA) .…”