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. Topical adapalene has poor systemic absorption and results in low blood levels (less than 0.025 mcg/L) even after 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. Interactions 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. Pharmacology 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. Pharmacokinetics 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 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. Pharmacodynamics Adapalene is highly lipophilic. When applied topically, it readily penetrates hair follicles and absorption occurs five 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