Penetration and percutaneous absorption of topical retinoids. A review

Topical retinoids are therapeutically active at low pharmaceutical concentrations, i.e. in essence lack of penetration is not a problem. Thus studies on the cutaneous pharmacokinetics focus on the distribution pattern in the skin, the penetration pathways, the cutaneous metabolism, the systemic body load and the mode of excretion. Two basically different pathways have to be taken into account: the transepidermal pathway, which gives rise to a typical epidermal/dermal concentration gradient and which is certainly part of the mode of action in disorders of keratinization, and the transfollicular pathway, which sheds some light on the activity in follicular disorders like acne. The cutaneous part of the pharmacokinetics of retinoids depends largely on their chemical structure and thus differs. However, common features are relatively high cutaneous concentrations, whereas the spillover to the systemic compartment appears to be slow and small, giving rise to low or hardly detectable bodyloads. Concerning pharmacokinetics topical application of retinoids presents major advantages over systemic medication. They can be targeted to the intended site of action, furthermore systemic toxicity is of much lesser concern.