Cross S E, Anderson C, Roberts M S
Department of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia.
Br J Clin Pharmacol. 1998 Jul;46(1):29-35. doi: 10.1046/j.1365-2125.1998.00045.x.
The penetration of active ingredients from topically applied anti-inflammatory pharmaceutical products into tissues below the skin is the basis of their therapeutic efficacy. There is still controversy as to whether these agents are capable of direct penetration by diffusion through the tissues or whether redistribution in the systemic circulation is responsible for their tissue deposition below the application site.
The extent of direct penetration of salicylate from commercial ester and salt formulations into the dermal and subcutaneous tissue of human volunteers was determined using the technique of cutaneous microdialysis. We also examined differences in the extent of hydrolysis of the methylester of salicylate applied topically in human volunteers and in vitro skin diffusion cells using full-thickness skin and epidermal membranes.
The present study showed that whilst significant levels of salicylate could be detected in the dermis and subcutaneous tissue of volunteers treated with the methylsalicylate formulation, negligible levels of salicylate were seen following application of the triethanolamine salicylate formulation. The tissue levels ofsalicylate from the methylsalicylate formulation were approx. 30-fold higher than the plasma concentrations.
The absorption and tissue concentration profiles for the commercial methylsalicylate formulation are indicative of direct tissue penetration and not solely redistribution by the systemic blood supply.
局部应用的抗炎药物产品中的活性成分渗透到皮肤以下组织是其治疗效果的基础。关于这些药物是能够通过组织扩散直接渗透，还是全身循环中的重新分布导致其在应用部位以下的组织沉积，仍存在争议。
采用皮肤微透析技术，测定商业酯类和盐类制剂中水杨酸盐对人类志愿者真皮和皮下组织的直接渗透程度。我们还研究了局部应用于人类志愿者和体外皮肤扩散细胞中的水杨酸甲酯在全层皮肤和表皮膜中的水解程度差异。
本研究表明，在用甲基水杨酸盐制剂治疗的志愿者的真皮和皮下组织中可检测到显著水平的水杨酸盐，而应用三乙醇胺水杨酸盐制剂后水杨酸盐水平可忽略不计。甲基水杨酸盐制剂的组织水杨酸盐水平约比血浆浓度高30倍。
商业甲基水杨酸盐制剂的吸收和组织浓度分布表明其可直接渗透到组织中，而不仅仅是通过全身血液供应重新分布。
