Cortexolone 17alpha-propionate

Cortexolone 17alpha-propionate Uses, Dosage, Side Effects, Food Interaction and all others data.

Cortexolone 17alpha-propionate (cortexolone 17α-propionate, CB-03-01) is a novel antagonist of androgen receptors. It binds to androgen receptors with high affinity. By competing with androgens for binding to androgen receptors, clascoterone works by blocking the androgen receptor signalling cascades that promote acne pathogenesis, such as sebaceous gland proliferation, excess sebum production, and inflammatory pathways. In August 2020, FDA approved clascoterone for the first-in-class topical treatment of acne (acne vulgaris) in male and female patients 12 years and older. Cortexolone 17alpha-propionate is also being investigated as a novel treatment for androgenetic alopecia.

Cortexolone 17alpha-propionate exerts anti-androgenic effects by working as an antagonist at androgen receptors (ARs) expressed throughout the skin, including sebaceous glands, sebocytes, and dermal papilla cells. Cortexolone 17alpha-propionate blocks the effects of testosterone and dihydrotestosterone (DHT), which are androgens that bind to the ARs and contribute to the development of androgen-dependent conditions such as acne and alopecia. In vitro, the antiandrogenic effects of clascoterone in human primary sebocytes occurred in a dose-dependent manner. Cortexolone 17alpha-propionate mediates selective topical activity by mainly targeting androgen receptors at the site of application. It has limited systemic effects.

In clinical trials, HPA axis suppression was observed as a 30-minute post-stimulation serum cortisol level of ≤18 mcg/dL in 5% of adult subjects and 9% of adolescent subjects with acne vulgaris following two weeks of topical treatment of clascoterone. HPA axis function returned to normal following the discontinuation of drug treatment.

Cortexolone 17alpha-propionate
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
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Interaction With other Medicine
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Trade Name	Cortexolone 17alpha-propionate
Generic	Clascoterone
Clascoterone Other Names	Clascoterone, Cortexolone 17alpha-propionate
Type
Formula	C₂₄H₃₄O₅
Weight	Average: 402.531 Monoisotopic: 402.240624195
Protein binding	Clascoterone is 84% to 89% bound to plasma proteins in vitro, regardless of drug concentrations.
Groups	Approved, Investigational
Therapeutic Class
Manufacturer
Available Country
Last Updated:	September 19, 2023 at 7:00 am

Uses

Cortexolone 17alpha-propionate is an androgen receptor antagonist used for the topical treatment of acne vulgaris in patients 12 years of age and older.

Cortexolone 17alpha-propionate is indicated for the topical treatment of acne vulgaris in patients 12 years of age and older.

Cortexolone 17alpha-propionate is also used to associated treatment for these conditions: Acne Vulgaris

How Cortexolone 17alpha-propionate works

Acne is a multifactorial skin condition characterized by excess sebum production, epithelial hyperkeratinization, proliferation of the skin commensal bacteria, and inflammation. Circulating and locally synthesized natural ligands, testosterone and dihydrotestosterone (DHT), serve as causative factors in both males and females. Upon binding of DHT, the DHT-androgen receptor complex dimerizes and translocates to the nucleus where it promotes the transcription of genes involved in acne pathogenesis, including proliferation and differentiation of sebocytes, excess sebum production, and inflammatory cytokine production. Cortexolone 17alpha-propionate is a potent antagonist at ARs and competes for androgens in binding to the receptor, thereby inhibiting downstream signalling of ARs that promote acne.

Androgenetic alopecia is also an androgen-dependent and highly genetic condition. Dihydrotestosterone (DHT) binds to ARs expressed on dermal papilla cells (DPC) in the scalp to induce AR-mediated transcription of genes that contribute to androgenic alopecia. By blocking the interaction between DHT and aARs, clascoterone inhibits AR-regulated transcription and DHT-induced IL-6 synthesis.

Toxicity

There is no information available on the toxicity profile of clascoterone, such as LD₅₀ and overdose in humans.

Food Interaction

No interactions found.

Volume of Distribution

There is no information available on the volume of distribution.

Elimination Route

Upon topical application, clascoteronet permeates the skin to the dermal levels with minimal systemic absorption. In clinical trials, adult subjects with moderate to severe facial acne vulgaris received twice-daily topical application of six grams of clascoterone. The steady-state concentrations of the drug were reached within five days. Following two weeks, the mean ± SD Cmax was 4.5 ± 2.9 ng/mL and the mean ± SD area under the plasma concentration-time over the dosing interval (AUCꞇ) was 37.1 ± 22.3 h*ng/mL. The mean ± SD average plasma concentration (Cavg) was 3.1 ± 1.9 ng/mL.