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Levoketoconazole, the 2s,4r enantiomer of ketoconazole, a new steroidogenesis inhibitor for Cushing’s Syndrome treatment

Journal of Clinical Endocrinology and Metabolism Jan 08, 2021

Creemers SG, Feelders RA, de Jong FH, et al. - This study was sought to correlate in vitro effects of levoketoconazole and racemic ketoconazole (RK) on adrenocortical and pituitary adenoma cells. Researchers incubated HAC15 cells and 15 primary human neoplastic adrenocortical cultures (+/- ACTH), and murine, and human corticotroph adenoma cultures with levoketoconazole or RK. They assessed cortisol and ACTH by applying a chemiluminescence immunoassay system, and steroid profiles by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In adrenocortical cells, levoketoconazole potently inhibits cortisol production, with a variable degree of suppression between specimens. Compared with RK, levoketoconazole inhibits adrenal steroid production more potently and might also inhibit ACTH secretion and growth of pituitary adenoma cells. Together with previously reported potential advantages, this demonstrates that for Cushing’s syndrome, levoketoconazole is a promising novel pharmacotherapy.

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