Topical penetration of commercial salicylate esters and salts using human isolated skin and clinical microdialysis studies
Topical penetration of commercial salicylate esters and salts using human isolated skin and clinical microdialysis studies
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DOI：
10.1046/j.1365-2125.1998.00045.x
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发表时间：
1998-07-01
影响因子：
3.4
通讯作者：
Roberts, MS
中科院分区：
文献类型：
--
作者：
Cross, SE;Anderson, C;Roberts, MS
目的外用抗炎药物的有效成分对皮肤以下组织的渗透是其治疗效果的基础。关于这些药物是否能够通过组织扩散直接渗透，或者在体循环中的再分布是否导致其在应用部位以下的组织沉积，仍存在争议。方法采用皮肤微透析技术，测定商品酯和盐制剂中的水杨酸盐在人体皮肤和皮下组织中的直接渗透程度。我们还检测了水杨酸甲酯在人类志愿者身上局部应用的不同程度，以及使用全层皮肤和表皮膜的体外皮肤扩散细胞。结果本研究表明，虽然使用水杨酸甲酯制剂的志愿者真皮和皮下组织中可以检测到显著水平的水杨酸盐，但使用三乙醇胺水杨酸酯制剂后，可以忽略不计的水杨酸盐水平。水杨酸甲酯制剂中的水杨酸盐的组织水平约为10%。结论市售水杨酸甲酯制剂的吸收和组织浓度曲线反映的是直接的组织渗透，而不仅仅是全身血供的再分布。
Aims 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.Methods 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.Results 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 of salicylate from the methylsalicylate formulation were approx. 30-fold higher than the plasma concentrations.Conclusion 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.