Trilostane

Trilostane

Systematic (IUPAC) name
(4α,5α,17β)-3,17-dihydroxy-4,5-epoxyandrost-2-ene-2-carbonitrile
Clinical data
AHFS/Drugs.com	monograph
Legal status	Veterinary use (U.S.)
Routes of administration	oral
Pharmacokinetic data
Metabolism	Hepatic
Biological half-life	8 hours
Identifiers
CAS Number	13647-35-3 N
ATC code	H02CA01 (WHO)
PubChem	CID: 656583
IUPHAR/BPS	6850
DrugBank	DB01108 Y
ChemSpider	570949 Y
UNII	L0FPV48Q5R Y
KEGG	D01180 Y
ChEBI	CHEBI:32260 Y
ChEMBL	CHEMBL1200907 N
Chemical data
Formula	C20H27NO3
Molecular mass	329.433 g/mol
SMILES N#C\C4=C(/O)[C@H]5O[C@]35[C@]([C@@H]2[C@H]([C@H]1[C@]([C@@H](O)CC1)(C)CC2)CC3)(C)C4
InChI InChI=1S/C20H27NO3/c1-18-7-6-14-12(13(18)3-4-15(18)22)5-8-20-17(24-20)16(23)11(10-21)9-19(14,20)2/h12-15,17,22-23H,3-9H2,1-2H3/t12-,13-,14-,15-,17+,18-,19+,20+/m0/s1 Y Key:KVJXBPDAXMEYOA-CXANFOAXSA-N Y
NY (what is this?)  (verify)

Trilostane is an inhibitor of 3 β-hydroxysteroid dehydrogenase used in the treatment of Cushing's syndrome.

It was withdrawn from human use in the United States market in April 1994. The drug was previously available in the United Kingdom for use in humans under the brand name Modrenal for the treatment of Cushing's disease and for breast cancer. It was approved in the United States in 2008 for the treatment of Cushing's disease (hyperadrenocorticism) in dogs under the brand name Vetoryl. It was available by prescription in the UK under the Vetoryl brand name for some time before it was approved in the US. The drug is also used to treat the skin disorder Alopecia X in dogs. It is also the first drug approved to treat both pituitary- and adrenal-dependent Cushing's in dogs. This prescription drug works by stopping the production of cortisol in the adrenal glands. In studies of the drug, the most common side effects were vomiting, lack of energy, diarrhea, and weight loss. Trilostane should not be given to a dog that:

1. has kidney or liver disease;
2. takes certain medications used to treat heart disease;
3. is pregnant, nursing or intended for breeding

The safety and effectiveness of trilostane were shown in several studies. Success was measured by improvements in both blood test results and physical symptoms (increased appetite and activity level, and decreased panting, thirst and urination).

Only one other drug, Anipryl (veterinary brand name) selegiline, is FDA-approved to treat Cushing's disease in dogs, but only to treat uncomplicated, pituitary-dependent Cushing's. The only previous treatment for the disease was the use of Mitotane (brand name Lysodren) off-label.

It has been used as a progesterone inhibitor.

A number of compounding pharmacies in the US sell the product. Since the US approval of Vetoryl in December 2008, compounding pharmacies are no longer able to use a bulk drug product for compounding purposes, but must prepare the compounded drug from Vetoryl.

It is a 3β-hydroxysteroid dehydrogenase inhibitor.

Chemistry

The compound is prepared from testosterone in a four-step synthesis.

External links

• Trilostane (Vetoryl) information from Veterinary Medicines Directorate, UK. Includes precautionary use regarding concurrent medical conditions, possible side effects, and possible interaction with other drugs. (PDF)