Evaluation of twice-daily, low-dose trilostane treatment administered orally in dogs with naturally occurring hyperadrenocorticism

Abstract

In dogs with NOH, administration of trilostane at low doses every 12 hours was effective, although 2 dogs became ill during treatment. Drug effects diminished within 8 to 9 hours. Because of potential adverse effects, lower doses should be evaluated.

Cortisol Concentrations in Well‐Regulated Dogs with Hyperadrenocorticism Treated with Trilostane

“…Results of this study suggest that in the population examined, serum cortisol concentrations measured before and after ACTH stimulation 9–12 hours after trilostane administration are significantly higher than those measured at 3–6 hours after trilostane administration. Although several other studies have documented that serum cortisol concentrations measured before and after ACTH stimulation are lower shortly after trilostane administration compared to several hours later, these studies examined a heterogeneous population of trilostane‐treated dogs with hyperadrenocorticism 2, 4, 7, 8. The present study is unique because it was performed in a particular subset of trilostane‐treated dogs with well‐regulated hyperadrenocorticism and low cortisol concentrations shortly after trilostane administration.…”

“…Serum cortisol concentrations before and after ACTH stimulation in trilostane‐treated dogs with hyperadrenocorticism are lower at 3 hours after trilostane administration compared to 9 hours after drug administration 4. However, this occurred in a mixed population of dogs including dogs with clinical signs indicative of poorly regulated hyperadrenocorticism and a wide range of serum cortisol concentrations before and after ACTH stimulation.…”

Comparison of Adrenocorticotropic Hormone Stimulation Test Results Started 2 versus 4 Hours after Trilostane Administration in Dogs with Naturally Occurring Hyperadrenocorticism

“…Veterinarians are instructed, in the literature, to begin ACTHst testing 2–24 hours after trilostane is administered to dogs with NOH 8, 9, 10, 11, 12, 13, 14, 15, 16. As demonstrated in an earlier study, ACTHst begun 3–4 hours after trilostane administration yielded significantly lower results when compared with tests begun 8–9 hours after 9.…”

“…If ACTHst results are utilized to aid in assessing trilostane dose, frequency of administration, or both, there is a question of when the test should be started relative to time of trilostane administration. In a previous study of dogs with NOH, post‐ACTH serum cortisol concentrations, when the test was started 8–9 hours posttrilostane administration (mean: 8.1 ± 3.4 μg/dL), significantly less inhibition of cortisol synthesis was demonstrated as compared with tests begun 3–4 hours after administration (mean: 2.6 ± 1.3 μg/dL) 9. One conclusion from that study was that results of the ACTHst started 3–4 hours after trilostane administration, in most dogs with NOH, were more indicative of trilostane's inhibition of cortisol synthesis than results from tests started 8–9 hours after administration 9…”

“…Among the suggested times to begin testing after trilostane administration are as follows: 2–3 hours,8 3 hours,9, 10 2–4 hours,11 2–5 hours,12 2–6 hours,13, 14 as long as 24 hours,15 and 4 hours if the drug is given once daily or 8–12 hours if the drug is given twice daily 16. The package insert that accompanies FDA‐approved trilostane recommends beginning ACTHst 4–6 hours after the drug has been administered 1…”