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Pharmacological particulars
Pharmacotherapeutic group: Antiadrenal preparations.
ATCvet code: QH02CA01.
Pharmacodynamic properties
Trilostane selectively and reversibly inhibits the enzyme system 3 beta hydroxysteroid isomerase, thus blocking the production of cortisol, corticosterone and aldosterone. When used to treat hyperadrenocorticism, it reduces the production of glucocorticoid and mineralocorticoid steroids in the adrenal cortex. Circulating concentrations of these steroids are thus reduced. Trilostane also antagonises the activity of exogenous adrenocorticotrophic hormone (ACTH). It has no direct effect on either the central nervous or cardiovascular systems.
Pharmacokinetic particulars
Pharmacokinetic data in dogs have demonstrated large inter-individual variability. In a pharmacokinetic study in laboratory beagles, AUC ranged from 52-281 micrograms/ml/min in fed dogs, and from 16-175 micrograms/ml/min in fasted dogs. Generally trilostane is rapidly removed from the plasma with concentrations in the plasma reaching a maximum between 0.5-2.5 hours and returning almost to baseline by six to twelve hours after administration. The primary active metabolite of trilostane, ketotrilostane follows a similar pattern. Furthermore, there was no evidence that trilostane or its metabolites accumulated with time. An oral bioavailability study in dogs demonstrated that trilostane was absorbed more extensively when administered with food.
Trilostane has been demonstrated to be excreted primarily in the faeces of the rat, indicating biliary excretion as the major metabolic pathway. In the monkey, trilostane is excreted in equal amounts in the faeces and urine. Results have shown that trilostane is rapidly and well absorbed from the gastrointestinal tract in both the rat and monkey and that it accumulates in the adrenal glands of the rat.