van Hoogdalem E J
Clinical Pharmacology Research Department, Yamanouchi Europe B.V., Leiderdorp, Netherlands.
J Eur Acad Dermatol Venereol. 1998 Sep;11 Suppl 1:S13-9; discussion S28-9. doi: 10.1111/j.1468-3083.1998.tb00902.x.
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.
寻常痤疮的药物治疗除口服药物外，还包括使用主要具有角质溶解作用的药物（如维甲酸和过氧化苯甲酰）以及抗生素（克林霉素、红霉素和红霉素 - 锌复合物）进行局部治疗。特定患者的痤疮分级通常决定首选给药途径的选择，即局部或口服，或两者结合，轻度至中度痤疮通常首选局部治疗。一般不考虑局部应用的化合物也可能在一定程度上被全身吸收这一事实。
本文综述了抗痤疮药物在人体经皮吸收的临床数据，以及它们与日常临床实践的相关性。
关于局部抗痤疮药物经皮渗透的大多数已发表数据集中在维甲酸类的维甲酸和抗菌药物克林霉素上。这种关注源于这些药物分别与胚胎毒性/致畸性和假膜性结肠炎有关。对于这两种化合物，局部应用后的全身吸收程度较低，最高分别为5 - 7%和8%。内源性维甲酸水平的高低和变异性很可能超过外源性应用维甲酸的任何贡献，但关于局部维甲酸在孕期安全使用仍缺乏完全共识。关于克林霉素，其局部使用与假膜性结肠炎发生之间的所谓关联似乎不具有临床相关性。为了尽可能减少全身暴露于克林霉素，磷酸克林霉素局部应用优于盐酸克林霉素盐。关于其他局部抗痤疮药物，从临床疗效和安全性角度来看，有人建议局部应用锌 - 红霉素优于红霉素。对于目前使用的化合物如过氧化苯甲酰、壬二酸和阿达帕林，现有的临床药代动力学数据很少，且尚未出现重大安全问题。
局部抗痤疮药物经皮吸收有限，这支持了它们在日常临床实践中的安全使用。关于局部维甲酸类药物在孕期的使用，缺乏正式共识。
