Pharmacokinetics and adverse effects of a long‐acting IM dopamine agonist: Cabergoline in healthy horses

Summary Background Pituitary pars intermedia dysfunction (PPID) is commonly treated with pergolide mesylate, a dopamine receptor agonist. Cabergoline is a dopamine receptor agonist that has shown activity on prolactin secretion in horses for up to 10 days. An injectable cabergoline formulation commercially available in the United States is a potential alternative treatment for PPID that could result in increased medication compliance due to the increased duration of activity and dose formulation. Objectives To investigate the pharmacokinetics and effects of i.m. cabergoline administration in healthy horses. Study design Experimental study with repeated measures. Methods Seven healthy adult geldings received a 0.011 mg/kg dose of cabergoline intramuscularly. Horses were monitored for adverse physical and neurological effects, changes in appetite, mentation and faeces. Blood samples were collected for pharmacokinetic analysis and plasma adrenocorticotropic hormone (ACTH) concentration at serial time points. Plasma cabergoline concentrations were assessed with liquid chromatography, and pharmacokinetic modelling was performed. Results Mean plasma ACTH concentrations decreased below 20 pg/mL by day five after cabergoline injection and did not increase above precabergoline injection concentrations after 19 days. Adverse effects included reduced appetite, sweat, mildly increased respiratory effort, loose faeces and lethargy. No other changes in physical examination parameters or neurologic abnormalities were noted. Mean C max for cabergoline was 1.46 ng/mL (±0.41 ng/mL), and mean T last was 75.4 h (±32.3 h). Main limitations The study group was small, composed of male horses with no control group. Conclusions The trend in plasma ACTH concentrations indicates that cabergoline has a prolonged effect on the pituitary gland after one dose. Adverse effects were like those reported with the administration of oral pergolide mesylate, with reduced appetite being notable. The lack of prolonged systemic adverse effects suggests cabergoline's relative safety for clinical use, although further studies are needed to assess cabergoline's effects in larger populations and in horses with PPID.