Transdermal absorption of topical anti-acne agents in man; review of clinical pharmacokinetic data

Background Apart from oral drug treatment, drug therapy in acne vulgaris co mprises topical treatment with agents with a primarily keratolytic action ( e.g. tretinoin and benzoylperoxide), and with antibiotics (clindamycin, ery thromycin, and erythromycin-zinc complex). The acne grade in the particular patient usually determines the selection of the preferred route of adminis tration, viz. topical or oral, or a combination of both, and topical treatm ent is usually preferred in mild to moderate acne. The fact that a topicall y applied compound may also become systemically available to a quantifiable extent, is not generally considered. Aim The present paper reviews the clinical data on transdermal uptake of an ti-acne agents in man, also with respect to their relevance for daily clini cal practice. Outcome The majority of published data on transdermaI penetration of topica l anti-acne agents focuses on the retinoid tretinoin, and on the antimicrob ial agent clindamycin. This interest emerges from the fact that these agent s have been associated with embryotoxicity/teratogenicity, and pseudomembra nous colitis, respectively. For both compounds the extent of systemic avail ability after topical application is low, viz. 5-7% and 8%, respectively, a t its highest. The height and variability in endogenous retinoid levels is very likely to outweigh any contribution of exogenously applied tretinoin, but a full consensus on the safe use of topical tretinoin in pregnancy is s till lacking. With respect to clindamycin, the suggested association betwee n its topical use and the occurrence of pseudomembranous colitis appears no t to be of clinical relevance. In order to reduce systemic exposure to clin damycin as much as possible, topical application of clindamycin phosphate i s to be preferred over clindamycin hydrochloride salt. Regarding other topi cal anti-acne agents. it has been suggested that topical zinc-erythromycin is to be preferred over erythromycin, both from clinical efficacy and safet y viewpoints. With respect to the currently used compounds like benzoylpero xide, azelaic acid, and adapalene, available clinical pharmacokinetic data are scarce, and significant safety concerns did not emerge as yet. Conclusion The limited transdermal uptake of topical anti-acne agents under pins their safe use in daily clinical practice. With respect to topical ret inoids, formal consensus is lacking regarding their use in pregnancy. (C) 1 998 Elsevier Science B.V. All rights reserved.