aminoglutethimide + ketoconazole

Aminoglutethimide + ketoconazole is a combination of two small molecule drugs, each with distinct but complementary mechanisms for suppressing steroid biosynthesis. Aminoglutethimide, originally developed as an anticonvulsant, inhibits several enzymes involved in corticosteroid synthesis and the aromatase enzyme responsible for converting androgens to estrogens. Ketoconazole, initially developed as an antifungal agent, also inhibits multiple steroidogenic enzymes—most notably C17,20-lyase—and has antiandrogenic and antiglucocorticoid effects. This combination is used off-label in the management of hormone-sensitive cancers (such as breast or prostate cancer) and endocrine disorders like Cushing's syndrome when monotherapy is insufficient to control cortisol levels[1][2][3]. The rationale for combining these agents lies in their synergistic suppression of adrenal steroidogenesis while potentially minimizing toxicity by allowing lower doses of each drug.