Active ingredient: Testolactone - Basic Profile / Key Facts

Basic Profile / Key Facts

Drug Category

• Antineoplastic Agents, Hormonal

Dosage Forms

• For oral administration as tablets providing 50 mg testolactone per tablet

Indications

For palliative treatment of advanced breast cancer in postmenopausal women.

Pharmacology

Testolactone is a synthetic anti-neoplastic agent that is structurally distinct from the androgen steroid nucleus in possessing a six-membered lactone ring in place of the usual five-membered carbocyclic D-ring. Despite some similarity to testosterone, testolactone has no in vivo androgenic effect. No other hormonal effects have been reported in clinical studies in patients receiving testolactone.

Mechanism of Action

Although the precise mechanism by which testolactone produces its clinical antineoplastic effects has not been established, its principal action is reported to be inhibition of steroid aromatase activity and consequent reduction in estrone synthesis from adrenal androstenedione, the major source of estrogen in postmenopausal women. Based on in vitro studies, the aromatase inhibition may be noncompetitive and irreversible. This phenomenon may account for the persistence of testolactone's effect on estrogen synthesis after drug withdrawal.

Absorption

Testolactone is well absorbed from the gastrointestinal tract.

Toxicity

Oral LD₅₀s in mouse and dog are 1630 mg/kg and 593-926 mg/kg, respectively.

Biotrnasformation / Drug Metabolism

Hepatic. Metabolized to several derivatives in the liver, all of which preserve the lactone D-ring.

Contraindications

Testolactone is contraindicated in the treatment of breast cancer in men and in patients with a history of hypersensitivity to the drug.

Drug Interactions

When administered concurrently, testolactone may increase the effects of oral anticoagulants; monitor and adjust anticoagulant dosage accordingly.

Drug/Laboratory Test Interactions:   Physiologic effects of testolactone may result in decreased estradiol concentrations with radioimmunoassays for estradiol, increased plasma calcium concentrations, and increased 24-hour urinary excretion of creatine and 17-ketosteroids.