ATCvet code: QH01AX90
Pharmacodynamics
Capromorelin is a selective ghrelin receptor agonist. Capromorelin binds to ghrelin receptors in the hypothalamus to stimulate appetite and in the pituitary to stimulate secretion of growth hormone (GH). Increased GH stimulates release of insulin like growth factor 1 (IGF-1) from the liver, which in turn stimulates weight gain.
The clinical effects of capromorelin in cats are a combination of increased food intake and metabolic changes resulting in weight gain.
In healthy cats, capromorelin increased food consumption, body weight and serum IGF-1 concentrations. In cats with chronic kidney disease and ≥5% unintended body weight loss, capromorelin increased body weight in the per protocol population by 6.8% compared to an untreated control group after 55 days of treatment (body weight loss of 1.7% in the control group and body weight gain of 5.1% in the capromorelin group).
Pharmacokinetics
Binding of capromorelin to cat plasma proteins was moderate (61%) over the assessed concentration range of 1 ng/ml to 100 ng/ml.
After oral administration, capromorelin was rapidly absorbed in cats with a Tmax of 0.35 hours (without food). The mean half-life of capromorelin in serum following intravenous and oral administration is 0.9 and 1.1 hours. Mean systemic clearance is 31.1 ml/min/kg body weight and mean apparent volume of distribution is 1.6 L/kg body weight. The short half-life can be attributed to the medium systemic clearance coupled with a medium volume of distribution. Administration of capromorelin with the entire daily ration compared to fasted cats led to increases in Tmax (1.25 versus 0.35 hours) and decreases in Cmax (28 versus 59 ng/ml) and AUC(0-last) (51 versus 83 ng.hour/ml). However, serum IGF-1 concentrations were increased by a similar amount when capromorelin was administered with or without food.
Serum concentrations of capromorelin increase proportionally with increasing dose over the range 1 - 4 mg/kg body weight as evidenced by an increase in mean Cmax and AUC and did not accumulate with repeated dosing over 10 days.