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 comprises topical treatment with agents with a primarily keratolytic action (e.g. tretinoin and benzoylperoxide), and with antibiotics (clindamycin, erythromycin, and erythromycin-zinc complex). The acne grade in the particular patient usually determines the selection of the preferred route of administration, viz. topical or oral, or a combination of both, and topical treatment is usually preferred in mild to moderate acne. The fact that a topically applied compound may also become systemically available to a quantifiable extent, is not generally considered.


OBJECTIVE
The present paper reviews the clinical data on transdermal uptake of anti-acne agents in man, also with respect to their relevance for daily clinical practice.


RESULTS
The majority of published data on transdermal penetration of topical anti-acne agents focuses on the retinoid tretinoin, and on the antimicrobial agent clindamycin. This interest emerges from the fact that these agents have been associated with embryotoxicity/teratogenicity, and pseudomembranous colitis, respectively. For both compounds the extent of systemic availability after topical application is low, viz. 5-7% and 8%, respectively, at 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 still lacking. With respect to clindamycin, the suggested association between its topical use and the occurrence of pseudomembranous colitis appears not to be of clinical relevance. In order to reduce systemic exposure to clindamycin as much as possible, topical application of clindamycin phosphate is to be preferred over clindamycin hydrochloride salt. Regarding other topical anti-acne agents, it has been suggested that topical zinc-erythromycin is to be preferred over erythromycin, both from clinical efficacy and safety viewpoints. With respect to the currently used compounds like benzoylperoxide, azelaic acid, and adapalene, available clinical pharmacokinetic data are scarce, and significant safety concerns did not emerge as yet.


CONCLUSIONS
The limited transdermal uptake of topical anti-acne agents underpins their safe use in daily clinical practice. With respect to topical retinoids, formal consensus is lacking regarding their use in pregnancy.
van Hoogdalem
E J
EJ
Clinical Pharmacology Research Department, Yamanouchi Europe B.V., Leiderdorp, Netherlands. hoogdalem.nl@yamanouchi-eu.com
D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000152:Acne Vulgaris / Q000188:drug therapy*; D000279:Administration, Cutaneous; D000284:Administration, Oral; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D002981:Clindamycin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D003879:Dermatologic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004761:Enterocolitis, Pseudomembranous / Q000139:chemically induced; D005260:Female; D006801:Humans; D007641:Keratolytic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D011247:Pregnancy; D012869:Skin Absorption; D014212:Tretinoin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D003879:Dermatologic Agents; D007641:Keratolytic Agents; D002981:Clindamycin; D014212:Tretinoin