Schaefer H, Stüttgen G, Zesch A, Schalla W, Gazith J
Curr Probl Dermatol. 1978;7:80-94. doi: 10.1159/000401278.
We have measured concentrations of about 30 drugs in the living layers of the skin under conditions which provide data which are applicable in therapeutic treatment. Since the skin is a thin organ and small amounts of drug represent high target concentrations, it is necessary to select a sensitive quantitative method; observation of the kinetics of absorption using radiolabeled drugs is the method of choice. Because of possible hazards--and legal and ethical problems--absorption studies in human skin are commonly performed in vitro. Related in vivo investigations demonstrate the relevance and the limitations of the in vitro experiments. The main hindrance against penetration of drugs is by the horny layer. The barrier-function of this layer--if it is undisturbed--may be described by a multilayer model. The reciprocal function, the reservoir function, is important for the efficiency of topical treatment; it also plays a role in determining the unique pharmacokinetics of drug absorption in the skin and percutaneous resorption. If the horny layer is injured, i.e. in diseased skin, both the barrier and the reservoir functions are disturbed. In consequence, drug concentrations in the skin--and percutaneous resorption--may be greatly enhanced, and topically applied drugs may enter preferentially into diseased areas. The form of application, such as ointment, solution, etc. influences the penetration kinetics in such a specific manner that a specific vehicle for a specific drug should always be postulated. The frequently discussed hazards of side effects due to percutaneous resorption of drugs like corticosteroids are a function of the treated area rather than of its penetration capacity. Thus the indication for local or oral treatment of severe dermatoses should be considered in terms of the affected area. The relatively frequent side effects in the skin itself which originate from unnecessarily high drug concentrations and long term treatment must also be taken into account.
我们已在能提供适用于治疗的数据的条件下，测量了皮肤活性层中约30种药物的浓度。由于皮肤是一个薄器官，少量药物就代表高靶浓度，因此有必要选择一种灵敏的定量方法；使用放射性标记药物观察吸收动力学是首选方法。由于可能存在的危害以及法律和伦理问题，人体皮肤吸收研究通常在体外进行。相关的体内研究证明了体外实验的相关性和局限性。药物渗透的主要障碍是角质层。如果该层的屏障功能未受干扰，可用多层模型来描述。其倒数功能，即储库功能，对局部治疗的效果很重要；它在决定皮肤药物吸收和经皮吸收的独特药代动力学方面也起作用。如果角质层受损，即在患病皮肤中，屏障和储库功能都会受到干扰。结果，皮肤中的药物浓度以及经皮吸收可能会大大提高，局部应用的药物可能会优先进入患病区域。给药形式，如软膏、溶液等，会以一种特定方式影响渗透动力学，以至于应始终为特定药物假定一种特定载体。像皮质类固醇等药物经皮吸收引起的副作用这一经常讨论的危害，是治疗面积的函数，而非其渗透能力的函数。因此，应根据受影响的面积来考虑严重皮肤病局部或口服治疗的适应症。还必须考虑到皮肤本身相对频繁的副作用，这些副作用源于不必要的高药物浓度和长期治疗。
