Wester R C, Maibach H I
Department of Dermatology, University of California School of Medicine, San Francisco.
Clin Pharmacokinet. 1992 Oct;23(4):253-66. doi: 10.2165/00003088-199223040-00002.
The skin is an evolutionary masterpiece of living tissue which is the final control unit for determining the local and systemic availability of any drug which must pass into and through it. In vivo in humans, many factors will affect the absorption of drugs. These include individual biological variation and may be influenced by race. The skin site of the body will also influence percutaneous absorption. Generally, those body parts exposed to the open environment (and to cosmetics, drugs and hazardous toxic substances) are most affected. Treating patients may involve single daily drug treatment or multiple daily administration. Finally, the body will be washed (normal daily process or when there is concern about skin decontamination) and this will influence percutaneous absorption. The vehicle of a drug will affect release of drug to skin. On skin, the interrelationships of this form of administration involve drug concentration, surface area exposed, frequency and time of exposure. These interrelationships determine percutaneous absorption. Accounting for all the drug administered is desirable in controlled studies. The bioavailability of the drug then is assessed in relationship to its efficacy and toxicity in drug development. There are methods, both quantitative and qualitative, in vitro and in vivo, for studying percutaneous absorption of drugs. Animal models are substituted for humans to determine percutaneous absorption. Each of these methods thus becomes a factor in determining percutaneous absorption because they predict absorption in humans. The relevance of these predictions to humans in vivo is of intense research interest. The most relevant determination of percutaneous absorption of a drug in humans is when the drug in its approved formulation is applied in vivo to humans in the intended clinical situation. Deviation from this scenario involves the introduction of variables which may alter percutaneous absorption.
皮肤是活组织进化的杰作,是决定任何必须透过它进入体内的药物局部和全身可用性的最终控制单元。在人体活体中,许多因素会影响药物的吸收。这些因素包括个体生物学差异,可能还受种族影响。身体的皮肤部位也会影响经皮吸收。一般来说,那些暴露于开放环境(以及化妆品、药物和有害有毒物质)的身体部位受影响最大。治疗患者可能涉及每日单次给药或每日多次给药。最后,身体会被清洗(日常正常过程或在担心皮肤去污时),这会影响经皮吸收。药物的载体将影响药物向皮肤的释放。在皮肤上,这种给药形式的相互关系涉及药物浓度、暴露的表面积、暴露频率和时间。这些相互关系决定经皮吸收。在对照研究中,考虑所有给药的药物是可取的。然后在药物研发中,根据药物的疗效和毒性评估其生物利用度。有体外和体内的定量和定性方法来研究药物的经皮吸收。用动物模型替代人体来确定经皮吸收。因此,这些方法中的每一种都成为决定经皮吸收的一个因素,因为它们预测人体的吸收情况。这些预测与人体活体情况的相关性是研究的热点。对人体药物经皮吸收最相关的测定是将已批准剂型的药物在预期临床情况下应用于人体活体。偏离这种情况会引入可能改变经皮吸收的变量。