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6 B. Zollers et al.
Fig. 7. Mean ( SD) cortisol serum levels on Day 1, Day 4 and Day 7 capromorelin-treated dogs. This study evaluated whether capro-
of treatment with capromorelin or placebo.
serum drug concentrations generally achieved within 30 min between dogs dosed at 3 mg/kg or 4.5 mg/kg once a day, indicat-
of administration. Although serum capromorelin concentra- ing that the 3 mg/kg dose is sufficient to keep IGF-1 serum con-
tions were highest in the 4.5 mg/kg capromorelin SID group, centrations high enough to attenuate the GH peak and also to
© 2016 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd
the clinical response to the drug, as measured by food con-
sumption and body weight, was similar for all treated groups.
The drug was well tolerated with few clinically observed effects.
The lethargy and soft stool observations could be the effects of
capromorelin on gastrointestinal motility. However, many factors
including the stress of multiple blood draws could result in these
observations, which were completed on the days these signs were
noted. The excessive salivation seen in dogs treated with capro-
morelin may be because of the bitter taste of the drug, although
flavorings were added to mask any bitterness. Alternatively, sali-
vation may be in response to the sensation of hunger which the
dogs may be experiencing as an action of capromorelin. In
humans, the ghrelin receptor has been shown to be present in
the salivary glands (Gr€ oschl et al., 2005), although this has not
been demonstrated in dogs, but if dog salivary glands also have
ghrelin receptors, it is possible that capromorelin could have a
direct effect on the salivary gland.
Food consumption increased as expected in the groups receiving
capromorelin. The percent change in food consumption was high-
est in dogs receiving 3.0 mg/kg once daily (Group 2), but mean
increases were seen in all capromorelin-treated groups. There was
a 13.5% decrease in food consumption in the control dogs. It is
unknown why the control group experienced a decrease in food
consumption, but it could be that the stress of an intensive bleed-
ing schedule on days 1, 4, and 7 affected food consumption. As
expected, the change in food consumption was directly related to
the change in body weight for all groups, and the amount of
weight gained in each capromorelin-treated group was significant.
There was no significant difference in the clinical response to
capromorelin dosed twice daily versus once daily or when using
3.0 mg/kg once daily versus 4.5 mg/kg once daily. Similarly, in
a masked, placebo-controlled, randomized clinical pilot study of
dogs with reduced appetite from a number of clinical conditions
(Zollers & Rhodes, 2014), it was shown that capromorelin given
at 4.5 mg/kg once-a-day improved owner assessment of appetite
and increased body weight over a 7-days treatment period.
After the first dose of capromorelin, the expected high peak of
GH was seen very quickly. This GH releasing action is expected
from a drug that binds the GHS receptor. It would not be desir-
able to stimulate the release of such a super-physiological
amount of GH chronically, and therefore, it is important that
over the 8 h after the first dose of capromorelin, the concentra-
tions of IGF-1 increase. This IGF-1 increase serves as negative
feedback, suppressing GH release. Clearly, by days 4 through 7
of dosing, the sustained elevation in IGF-1 concentrations seen
in the capromorelin-treated dogs result in an attenuation of the
GH spike observed after the dose of capromorelin is administered.
To maintain this negative feedback suppression of the GH
release, IGF-1 serum concentrations need to remain elevated in
morelin needed to be dosed once or twice a day to maintain ele-
vated serum IGF-1 concentrations, and the data clearly show that
once-a-day dosing is sufficient. Further, there was no difference