Department of Medicine, University of Queensland, Princess Alexandra Hospital, 4102, Brisbane, Queensland, Australia.
Inflammopharmacology. 1999;7(4):339-50. doi: 10.1007/s10787-999-0028-6.
Topical NSAIDS and related solutes are often applied to the skin to target tissues directly below the application site. We have used both biopsy and microdialysis techniques to show that most solutes penetrate below dermal capillaries into the subcutaneous and deeper tissues of both rats and human subjects. The selectivity of local penetration is time related, the concentrations in underlying tissues at longer times often being defined by recirculation from the systemic blood supply. Increased depths of penetration may be achieved by the use of vasoactive agents. Iontophoretic and other delivery systems appear to increase the efficiency of drug delivery through the stratum corneum and do not appear to greatly facilitate penetration into tissues below the dermis. Vehicle polarity and solute properties such as size can be used to advantage in delivering NSAIDs to deeper tissues.The pharmacokinetics of NSAIDs in the dermis and other tissues appears to be related to the absorption of solutes through the stratum corneum, binding of the NSAIDs to dermal and other tissues and clearance of NSAIDs from these tissues through either diffusion into deeper tissues or removal by the systemic blood supply. The latter is dependent on the blood flow to the tissues and protein binding of the NSAIDs in the blood. Absorption of NSAIDs and other solutes through the stratum corneum is defined by their inherent hydrogen bonding ability, lipophilicity and size as well as the interactions between the solute, vehicle and skin.The literature contains a number of examples of pharmacological efficacy after topical application which can now be better explained in terms of our recently gained understanding of the pharmacokinetics of NSAIDs after topical application. A complicating aspect in this interpretation is the variation in efficacy between the various models used to date.
局部用 NSAIDs 和相关溶质通常被应用于皮肤，以直接靶向应用部位下方的组织。我们已经使用活检和微透析技术表明，大多数溶质穿透真皮毛细血管进入大鼠和人体受试者的皮下和更深层组织。局部穿透的选择性与时间有关，较长时间内皮下组织中的浓度通常由来自全身血液供应的再循环决定。通过使用血管活性剂，可以实现穿透深度的增加。离子电渗和其他传递系统似乎增加了药物通过角质层的传递效率，而不会极大地促进真皮以下组织的穿透。载体极性和溶质性质（如大小）可用于将 NSAIDs 递送至更深层的组织。NSAIDs 在真皮和其他组织中的药代动力学似乎与溶质通过角质层的吸收有关，与 NSAIDs 与真皮和其他组织的结合以及 NSAIDs 通过扩散到更深层组织或通过全身血液供应从这些组织中清除有关。后者取决于组织的血流量和血液中 NSAIDs 的蛋白结合。NSAIDs 和其他溶质通过角质层的吸收取决于其内在的氢键形成能力、亲脂性和大小以及溶质、载体和皮肤之间的相互作用。文献中有许多局部应用后药理学疗效的例子，现在可以根据我们最近对 NSAIDs 局部应用后药代动力学的理解更好地解释。在这种解释中，一个复杂的方面是迄今为止使用的各种模型之间疗效的差异。
