Levoketoconazole: a novel treatment for endogenous Cushing's syndrome.

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Fleseriu M, Auchus RJ, Pivonello R, Salvatori R, Zacharieva S, Biller BMK

Levoketoconazole: a novel treatment for endogenous Cushing's syndrome.

Expert Rev Endocrinol Metab. 2021 Jul;16(4):159-174. doi: 10.1080/17446651.2021.1945440. Epub 2021 Aug 12.

PubMed ID

34380370 [ View in PubMed

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Abstract

Introduction: Endogenous Cushing's syndrome (CS) is a rare, life-threatening endocrine disorder that is caused by chronic exposure to cortisol overproduction. Levoketoconazole (Recorlev), a 2S, 4R stereoisomer of ketoconazole, is a steroidogenesis inhibitor under investigation for the treatment of CS.Areas covered: This review covers the pharmacology, efficacy, and safety of levoketoconazole for the treatment of patients with endogenous CS.Expert opinion: Based on the preclinical and clinical pharmacology findings, levoketoconazole appears to be the relevant enantiomer of ketoconazole for inhibition of steroidogenesis, with more potent inhibition of both cortisol and androgen synthesis relative to ketoconazole racemate and the 2R, 4S stereoisomer dextroketoconazole. Results from the phase III SONICS study showed that levoketoconazole was effective in normalizing cortisol levels and improving biomarkers of cardiovascular risk in a significant percentage of patients. In addition, treatment with levoketoconazole showed improvements in subjective clinical assessments of clinician-rated CS clinical signs and symptoms, patient-reported quality of life, and depression symptom severity. Testosterone levels decreased significantly in women. Levoketoconazole had an acceptable safety profile with no unexpected safety signals. The favorable pharmacology, efficacy, and safety profile of levoketoconazole supports its use as medical therapy for CS, if approved.

DrugBank Data that Cites this Article

Drugs

Levoketoconazole

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Levoketoconazole	Cholesterol side-chain cleavage enzyme, mitochondrial	Protein	Humans	Yes	Inhibitor	Details
Levoketoconazole	Cytochrome P450 11B1, mitochondrial	Protein	Humans	Yes	Inhibitor	Details
Levoketoconazole	Cytochrome P450 11B2, mitochondrial	Protein	Humans	Yes	Inhibitor	Details
Levoketoconazole	Lanosterol 14-alpha demethylase	Protein	Humans	No	Inhibitor	Details
Levoketoconazole	Steroid 17-alpha-hydroxylase/17,20 lyase	Protein	Humans	Yes	Inhibitor	Details