Guy R H, Hadgraft J
Department of Pharmacy, University of California, San Francisco 94143.
Pharm Res. 1988 Dec;5(12):753-8. doi: 10.1023/a:1015980516564.
The classic diffusion model-based interpretation of percutaneous absorption is compared to a simple kinetic analysis. The physicochemical significance and the major deductions of the two approaches are shown to be in general agreement. In particular, the effect of penetrant oil/water partition coefficient on transdermal flux is consistently predicted by the two models. Diffusional and kinetic assessments of skin penetration enhancement are then shown to reveal similar dependencies upon penetrant physical chemistry. It is demonstrated that the requirements for successful promotion of a lipophilic drug's transdermal flux are quite different from those necessary for a hydrophilic penetrant. Finally, in light of published transport data and our increased comprehension of the stratum corneum barrier function, the evidence for (and significance of) different absorption paths across the stratum corneum is considered. In addition, the impact of penetrant "size" on transport is addressed. It is argued that currently held beliefs concerning (i) a putative "polar" route through the stratum corneum and (ii) the dependence of flux on molecular weight warrant considerable further attention before their unequivocal acceptance is appropriate.
将基于经典扩散模型的经皮吸收解释与简单动力学分析进行了比较。结果表明，这两种方法的物理化学意义和主要推论总体上是一致的。特别是，两种模型都一致预测了渗透剂油/水分配系数对透皮通量的影响。随后表明，对皮肤渗透增强的扩散和动力学评估揭示了对渗透剂物理化学的相似依赖性。结果表明，成功促进亲脂性药物透皮通量的要求与亲水性渗透剂所需的要求有很大不同。最后，根据已发表的转运数据以及我们对角质层屏障功能的进一步理解，考虑了穿过角质层的不同吸收途径的证据（及其意义）。此外，还讨论了渗透剂“大小”对转运的影响。有人认为，目前关于（i）穿过角质层的假定“极性”途径和（ii）通量对分子量的依赖性的观点，在明确接受之前需要相当多的进一步关注。
