Surber C, Wilhelm K P, Maibach H I
Department of Dermatology, University of California, San Francisco.
Arzneimittelforschung. 1993 Sep;43(9):1001-4.
The oral administration of retinoids such as etretinate and acitretin (Ro 10-1670, CAS 55079-83-9), provides a successful therapeutic approach in various cutaneous diseases characterized by disturbed keratinization, e.g. psoriasis. Nevertheless oral therapy is often associated with systemic adverse effects. This makes a topical form with no or reduced systemic side effects desirable. Direct application of a topical acitretin formulation to the skin might result in therapeutic skin concentrations while minimizing systemic exposure. In the hairless guinea pig and in the rhesus monkey the percutaneous absorption of [14C]acitretin from an isopropylmyristate formulation (160 micrograms acitretin/2.5 cm2/animal) were investigated in vivo. After a 24 h exposure drug concentration in the skin was higher in the hairless guinea pig (620 ng-eq/g wet tissue) than in the rhesus monkey (380 ng-eq/g wet tissue). A similar observation was made comparing the 24 h absorption data determined as amount of drug excreted. The results are compared with in vitro absorption data using skin from the same species.
口服维甲酸类药物，如依曲替酯和阿维A（Ro 10-1670，CAS 55079-83-9），为治疗各种以角化异常为特征的皮肤疾病（如银屑病）提供了一种成功的治疗方法。然而，口服治疗常常伴有全身性不良反应。这使得人们期望有局部用药形式，其全身副作用无或减少。将局部用阿维A制剂直接应用于皮肤可能会达到治疗性皮肤浓度，同时使全身暴露最小化。在无毛豚鼠和恒河猴体内研究了[14C]阿维A从肉豆蔻酸异丙酯制剂（160微克阿维A/2.5平方厘米/动物）的经皮吸收情况。暴露24小时后，无毛豚鼠皮肤中的药物浓度（620纳克当量/克湿组织）高于恒河猴（380纳克当量/克湿组织）。比较以药物排泄量确定的24小时吸收数据时也有类似观察结果。将这些结果与使用相同物种皮肤的体外吸收数据进行了比较。
