|Trade names||Differin, Pimpal, Gallet, Adelene, Adeferin|
|Bioavailability||Very low[medical citation needed]|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||412.529 g·mol−1|
|3D model (JSmol)|
Adapalene is a third-generation topical retinoid primarily used in the treatment of mild-moderate acne, and is also used off-label to treat keratosis pilaris as well as other skin conditions. Studies have found adapalene is as effective as other retinoids, while causing less irritation. It also has several advantages over other retinoids. The adapalene molecule is more stable compared to tretinoin and tazarotene, which leads to less concern for photodegradation. It is also chemically more stable compared to the other two retinoids, allowing it to be used in combination with benzoyl peroxide. Due to its effects on keratinocyte proliferation and differentiation, adapalene is superior to tretinoin for the treatment of comedonal acne and is often used as a first-line agent. 
Per the recommendations of the Global Alliance on Improving Outcomes of Acne, retinoids such as adapalene are considered first-line therapy in acne treatment and are to be used either independently or in conjunction with benzoyl peroxide and/or an antimicrobial agent, like clindamycin, for maximum efficacy. Furthermore, adapalene, like other retinoids, increases the efficacy and penetration of other topical acne medications that are used in conjunction with topical retinoids as well as hastens the improvement of the post-inflammatory hyperpigmentation caused by acne. In the long term, it can be used as maintenance therapy.
Adapalene has the unique ability to inhibit keratinocyte differentiation and decrease keratin deposition. This property makes adapalene an effective treatment for keratosis pilaris and callus. It may be used by men undergoing foreskin restoration to reduce excess keratin that forms a layer on the exterior of the human penis after circumcision. Other non-FDA approved indications that have been reported in the literature include treatment of warts, molluscum contagiosum, Darier disease, photoaging, pigmentary disorders, actinic keratoses and alopecia areata.
Adapalene is known to cause mild adverse effects such as photosensitivity, irritation, redness, dryness, itching, and burning. It is common (between 1% and 10% of users) to experience a brief sensation of warmth or stinging, as well as dry skin, peeling and redness during the first 2–4 weeks of using the medication. These effects are considered mild and generally decrease over time. Any serious allergic reaction is rare. Furthermore, of the three topical retinoids, adapalene is often regarded as the most tolerable.
Use of topical adapalene in pregnancy has not been well studied, but has a theoretical risk of retinoid embryopathy. Thus far, there is no evidence that the cream causes problems in the baby if used during pregnancy. Use is at the consumer's own risk.
According to the Drugs and Lactation Database, topical adapalene has poor systemic absorption and results in low blood levels (less than 0.025 mcg/L) despite long term use, suggesting that there is low risk of harm for a nursing infant. However, it is recommended that the topical medication should not be applied to the nipple or any other area that may come into direct contact with the infant's skin.
Adapalene has been shown to enhance the efficacy of topical clindamycin, although adverse effects are also increased. Application of adapalene gel to the skin 3–5 minutes before application of clindamycin enhances penetration of clindamycin into the skin, which may enhance the overall efficacy of the treatment as compared to clindamycin alone.
Unlike the retinoid tretinoin (Retin-A), adapalene has also been shown to retain its efficacy when applied at the same time as benzoyl peroxide due to its more stable chemical structure. Furthermore, photodegradation of the molecule is less of a concern in comparison to tretinoin and tazarotene.
Absorption of adapalene through the skin is low. A study with six acne patients treated once daily for five days with two grams of adapalene cream applied to 1,000 cm2 (160 sq in) of skin found no quantifiable amounts, or less than 0.35 ng/mL of the drug, in the patients' blood plasma. Controlled trials of chronic users of adapalene have found drug levels in the patients' plasma to be 0.25 ng/mL.
Adapalene is highly lipophilic. When applied topically, it readily penetrates hair follicles and absorption occurs 5 minutes after topical application. After penetration into the follicle, adapalene binds to nuclear retinoic acid receptors (namely retinoic acid receptor beta and gamma). These complexes then bind to the retinoid X receptor which induces gene transcription by binding to specific DNA sites, thus modulating downstream keratinocyte proliferation and differentiation. This results in normalization of keratinocyte differentiation, allowing for decreased microcomedone formation, decreased clogging of pores, and increased exfoliation by increasing cell turnover. Adapalene is also regarded as an anti-inflammatory agent, as it suppresses the inflammatory response stimulated by the presence of Cutibacterium acnes, and inhibits both lipoxygenase activity and the oxidative metabolism of arachidonic acid into prostaglandins.
Adapalene selectively targets retinoic acid receptor beta and retinoic acid receptor gamma when applied to epithelial cells such as those found in the skin. Its agonism of the gamma subtype is largely responsible for adapalene's observed effects. In fact, when adapalene is applied in conjunction with a retinoic acid receptor gamma antagonist, adapalene loses clinical efficacy.
Retinization is a common temporary phenomenon reported by patients when initiating use of retinols. Within the initial period of treatment, skin can become red, irritated, dry and may burn or itch from retinol application; however, this tends to resolve within four weeks with once a day use.
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