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

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 Cl-area, Vd(area) and T-1/2 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 Cl-area/F, Vd(area)/F and T-1/2 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.