tretinoin and Enterocolitis--Pseudomembranous

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.. 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.. 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.. 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.

Topics: Abnormalities, Drug-Induced; Acne Vulgaris; Administration, Cutaneous; Administration, Oral; Anti-Bacterial Agents; Clindamycin; Dermatologic Agents; Drug Therapy, Combination; Enterocolitis, Pseudomembranous; Female; Humans; Keratolytic Agents; Pregnancy; Skin Absorption; Tretinoin

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Cells; Enterocolitis, Pseudomembranous; Humans; Idarubicin; Leukemia, Promyelocytic, Acute; Male; Mercaptopurine; Methotrexate; Necrosis; Recovery of Function; Remission Induction; Tretinoin; Vancomycin

Syrian hamsters are exquisitely sensitive to clindamycin; as little as 1 mg/kg of clindamycin given systemically causes a fatal colitis. Clindamycin and erythromycin were applied topically daily to the shaved backs of Syrian hamsters in a hydroalcoholic vehicle. A daily dose of 0.1 mg of clindamycin was lethal to more than half the hamsters and 1 mg to all the animals. The antibiotic-associated toxin from Clostridium difficile was present in their cecal material. Based on body surface areas and estimated usual volumes applied, the lethal dose in hamsters is not dissimilar to that given humans for acne. Oral tetracycline therapy protected the animals from clindamycin toxicity, but the animals died three days after stopping tetracycline if topical clindamycin applications were continued.

Topics: Administration, Topical; Animals; Clindamycin; Clostridium Infections; Cricetinae; Enterocolitis, Pseudomembranous; Erythromycin; Humans; Male; Mesocricetus; Tretinoin