Adapalene

Absorption

Adapalene is applied topically and absorbed through the skin. In one clinical study treating patients once per day with 2g of 0.3% gel applied to 2 mg/cm2 of skin, 15 patients had detectable blood plasma adapalene levels (0.1 ng/ml) resulting in a mean Cmax of 0.553 ± 0.466 ng/ml and a mean AUC of 8.37 ± 8.46 ng*h/ml on day 10.

Toxicity

Toxicity information regarding adapalene is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as redness, scaling, and skin discomfort. Symptomatic and supportive measures are recommended.
Adapalene has an acute oral LD50 in S-D rats and CD-1 mice of over 5000 mg/kg. The LD50 of 0.3% applied topically to Credo OF1 mice is over 10 ml/kg (30 mg/kg). No systemic or local toxicity was observed in rats treated topically with 6 mg/kg/day of 0.3% adapalene.

Description

Adapalene is a synthetic retinoid and an agonist of retinoic acid receptors (RARs; K_ds = 1,100, 34, and 130 nM for RARα, RARβ, and RARγ, respectively). It inhibits growth and differentiation of sebocytes in a concentration-dependent manner in primary rat preputial cell culture. Adapalene (10 μM) completely inhibits the activity of soybean 15-lipoxygenase (15-LOX) in an enzyme assay and inhibits the 5- and 15-LOX pathways in human blood polymorphonuclear leukocytes (PMNs). It reduces the protein levels of toll-like receptor 2 (TLR2) and IL-10 in skin explants isolated from patients with acne and healthy controls in a concentration-dependent manner but increases the expression of the antigen-presenting protein CD1d in acne skin explants while decreasing it in control explants. It inhibits inflammation in rodent models of ear edema induced by arachidonic acid and carrageenan-induced paw edema. Adapalene (100 μM) also induces apoptosis and inhibits proliferation of CC-531, HT-29, and LoVo colon cancer cells and reduces tumor growth in a DLD-1 colon cancer nude mouse xenograft model in a dose-dependent manner. Formulations containing adapalene have been used in the treatment of acne vulgaris.

Description

Adapalene, is in a class of retinoid-like compounds used to control acne. It is believed that, by binding with specific receptors in the skins cells, adapalene encourages the growth of healthy skin cells and reduces the development of acne lesions.

The Uses of Adapalene

Adapalene has been used as a retinoic acid receptor (RAR) agonist to study its effects on inhibiting transcription of hepatitis B virus in covalently closed circular DNA (cccDNA). It has also been used as a component to culture mixed lymphocyte reactions (MLR) to study its effects on isolated macrophages.

What are the applications of Application

Adapalene is a retinoic acid analog and apoptosis inducer

Background

Acne vulgaris is a multifactorial disorder of the pilosebaceous unit involving increased sebum production, inflammation, and hyperproliferation/hyperkeratinization of the follicular infundibulum. It is also associated with Cutibacterium acnes (also known as Propionibacterium acnes). Adapalene is a third-generation topical retinoid used for the treatment of acne vulgaris. Adapalene has similar efficacy but a superior safety profile compared to tretinoin. Tazarotene is more efficacious than adapalene but is designated as pregnancy category X and hence is contraindicated in pregnant women. Adapalene can also be combined with benzoyl peroxide (BPO), which possesses bactericidal properties, and either adapalene alone, or adapalene BPO combination products, are commonly used to treat mild-to-severe acne.
Differin?, produced by Galderma Labs, was first granted FDA approval on May 31st, 1996, as a 0.1% adapalene topical solution. Differin was later made available as 0.1% gel, cream, or lotion, or 0.3% gel products. On December 8th, 2008, Galderma Labs gained FDA approval for Epiduo?, a 0.1% adapalene, 2.5% BPO combination gel.

Indications

Adapalene is indicated for the topical treatment of acne vulgaris in patients aged 12 and over. It is also indicated for acne vulgaris in combination with benzoyl peroxide and in a triple combination therapy with benzoyl peroxide and clindamycin.

Pharmacokinetics

Adapalene is anticomedogenic, preventing the formation of new comedones and inflammatory lesions, and also acts to reduce inflammation by modulating the innate immune response. Like other retinoid compounds, adapalene is chemically stable but photosensitive; use with sunscreen is recommended. Minor skin irritations, including erythema, scaling, dryness, and stinging/burning, have been reported.

Metabolism

Extensive information regarding adapalene metabolism in humans is unavailable, although it is known to accumulate in the liver and GI-tract. In human, mouse, rat, rabbit, and dog cultured hepatocytes, metabolism appears to affect the methoxybenzene moiety but remains incompletely characterized. The major products of metabolism are glucuronides. Approximately 25% of the drug is metabolized; the rest is excreted as parent drug.