Objective—To determine whether trilostane or ketotrilostane is more potent in dogs and determine the trilostane and ketotrilostane concentrations that inhibit adrenal gland cortisol, corticosterone, and aldosterone secretion by 50%.
Sample—24 adrenal glands from 18 mixed-breed dogs.
Procedures—Adrenal gland tissues were sliced, placed in tissue culture, and stimulated with 100 pg of ACTH/mL alone or with 5 concentrations of trilostane or ketotrilostane. Trials were performed independently 4 times. In each trial, 6 samples (1 for each time point) were collected for each of the 5 concentrations of trilostane and ketotrilostane tested as well as a single negative control samples. At the end of 0, 1, 2, 3, 5, and 7 hours, tubes were harvested and media and tissue slices were assayed for cortisol, corticosterone, aldosterone, and potassium concentrations. Data were analyzed via pharmacodynamic modeling. One adrenal slice exposed to each concentration of trilostane or ketotrilostane was submitted for histologic examination to assess tissue viability.
Results—Ketotrilostane was 4.9 and 2.4 times as potent in inhibiting cortisol and corticosterone secretion, respectively, as its parent compound trilostane. For trilostane and ketotrilostane, the concentrations that inhibited secretion of cortisol or corticosterone secretion by 50% were 480 and 98.4 ng/mL, respectively, and 95.0 and 39.6 ng/mL, respectively.
Conclusions and Clinical Relevance—Ketotrilostane was more potent than trilostane with respect to inhibition of cortisol and corticosterone secretion. The data should be useful in developing future studies to evaluate in vivo serum concentrations of trilostane and ketotrilostane for efficacy in the treatment of hyperadrenocorticism.
Objective—To assess serum 17-α-hydroxyprogesterone
(17OHP) and corticosterone concentrations in
dogs with nonadrenal neoplasia and dogs being
screened for hyperadrenocorticism.
Animals—16 clinically normal dogs, 35 dogs with
nonadrenal neoplasia, and 127 dogs with suspected
Procedure—ACTH stimulation tests were performed
in all dogs. Baseline serum cortisol and corticosterone
concentrations were measured in the healthy dogs;
baseline serum cortisol concentration and ACTH-stimulated
cortisol, corticosterone, and 17OHP concentrations
were measured in all dogs. Endogenous plasma
ACTH concentration was also measured before
administration of ACTH in dogs with neoplasia.
Results—In 35 dogs with neoplasia, 31.4% had high
serum 17OHP concentration and 22.9% had high
serum corticosterone concentration. Of the 127 dogs
with suspected hyperadrenocorticism, 59 (46.5%) had
high ACTH-stimulated cortisol concentrations; of those,
42 of 59 (71.2%) and 32 of 53 (60.4%) had high serum
17OHP and corticosterone concentrations, respectively.
Of dogs with serum cortisol concentration within reference
range after ACTH administration, 9 of 68 (13.2%)
and 7 of 67 (10.4%) had high serum 17OHP and corticosterone
concentrations, respectively. In the dogs
with neoplasia and dogs suspected of having hyperadrenocorticism,
post-ACTH serum hormone concentrations
were significantly correlated.
Conclusions and Clinical Relevance—Serum concentrations
of 17OHP or corticosterone after administration
of ACTH may be high in dogs with nonadrenal neoplasia
and no evidence of hyperadrenocorticism. Changes in
serum 17OHP or corticosterone concentrations after
administration of ACTH are proportionate with changes
in cortisol concentration. (J Am Vet Med Assoc 2005;227:1762–1767)
OBJECTIVE To determine whether 2- or 3-times-daily application of topical ophthalmic 0.005% latanoprost solution is more effective at lowering intraocular pressure (IOP) in clinically normal dogs.
ANIMALS 9 clinically normal dogs.
PROCEDURES For each dog, I drop of latanoprost 0.005% solution was applied to 1 eye every 8 or 12 hours each day for 5 days; the contralateral eye received topical ophthalmic treatment with 1 drop of saline (0.9% NaCl) solution at the times of latanoprost application. Ocular examinations of both eyes were performed every 6 hours starting 48 hours prior to and ending 42 hours after the treatment period. Following a 5-week washout interval, the procedures were repeated but the previously latanoprost-treated eye of each dog received latanoprost application at the alternate frequency.
RESULTS Mean ± SD IOP reduction in the latanoprost-treated eyes was 31 ± 6.9% with 2-times-daily application and 33 ± 8.2% with 3-times-daily application. A 2-way repeated-measures ANOVA revealed significant differences in IOP with contributions by treatment (2 or 3 times daily), time of day (diurnal variation), and individual dog. The maximum mean daily IOP reduction in latanoprost-treated eyes was detected on day 3 of latanoprost treatment in each group. Eyes treated 3 times daily had significantly smaller pupil diameter and greater conjunctival hyperemia than eyes treated 2 times daily.
CONCLUSIONS AND CLINICAL RELEVANCE The clinical importance of the ocular hypotensive effects of 3-times-daily topical ophthalmic application of 0.005% latanoprost solution in dogs with glaucoma warrants investigation.