Trilostane 13647-35-3

Trilostane (CAS 13647-35-3) is a competitive inhibitor of 3β-hydroxysteroid dehydrogenase, the enzyme responsible for cortisol synthesis in the adrenal cortex. In veterinary medicine it is the first-line pharmacotherapy for canine hyperadrenocorticism (Cushing’s disease), both pituitary-dependent and adrenal-dependent forms. Marketed as Vetoryl, trilostane has largely replaced mitotane (o,p’-DDD) as the preferred medical management option due to its reversible mechanism of action and more predictable safety profile in dogs.

Veterinary Pharmacology

Trilostane suppresses cortisol production by blocking the conversion of pregnenolone to progesterone. In dogs with pituitary-dependent hyperadrenocorticism (PDH), which accounts for approximately 80-85% of naturally occurring Cushing’s cases, trilostane achieves clinical improvement in polydipsia, polyuria, polyphagia, and dermatological signs within 2-4 weeks of initiating therapy. ACTH stimulation testing is used to monitor therapeutic response, with target post-ACTH cortisol levels typically between 40-150 nmol/L (1.45-5.4 μg/dL).

Species-Specific Dosing

Dogs: Initial dose 1-2 mg/kg orally once daily, administered with food to improve bioavailability. Dose titration guided by ACTH stimulation tests performed at 10-14 days, 30 days, 90 days, and every 3-6 months thereafter. Some dogs require twice-daily dosing (split total daily dose) for adequate cortisol suppression over 24 hours. Maximum recommended dose: 10 mg/kg/day. Dose adjustments should not exceed 50% of the current dose at any single re-evaluation.

Cats: Off-label use at 30 mg per cat once to twice daily has been reported for feline hyperadrenocorticism, though surgical adrenalectomy remains the preferred treatment in cats when feasible.

Regulatory & Pharmacopeia References

Trilostane is licensed for veterinary use in dogs in the EU (EMA), USA (FDA-CVM, NADA 141-291), UK (VMD), and numerous other jurisdictions. The European Pharmacopoeia (Ph. Eur.) monograph provides quality specifications for trilostane as a veterinary API. This product was withdrawn from human use in the USA in 1994; its primary global application is now exclusively veterinary.