Pimecrolimus permeates less than tacrolimus through normal, inflamed, or corticosteroid-pretreated skin
Pimecrolimus permeates less than tacrolimus through normal, inflamed, or corticosteroid-pretreated skin
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DOI：
10.1111/j.1600-0625.2005.00354.x
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发表时间：
2005-10-01
影响因子：
3.6
通讯作者：
Billich, A
中科院分区：
文献类型：
--
作者：
Meingassner, JG;Aschauer, H;Billich, A
采用Franz型扩散池，在体外比较了正常人和正常、发炎或皮质类固醇（CS）预处理的年轻家猪皮肤对吡美莫司和他克莫司的渗透性。供试品以1.0%溶液或市售制剂（Elidel 1%乳膏、Protopic 0.1%和0.03%软膏）的形式使用。在正常人皮肤中，吡美莫司从1%乳膏中的渗透率比他克莫司从0.1%软膏中的渗透率低约6倍，比他克莫司从0.03% Protopic中的渗透率低4.3倍。在猪中，十二烷基硫酸钠诱导的刺激性接触性皮炎导致两种药物从应用溶液中的皮肤渗透显著加快。吡美莫司的渗透速率低于他克莫司。因此，在24小时，接受液中吡美莫司浓度比他克莫司水平低2.8倍。与正常猪皮肤相比，药物通过氢化可的松（1.0%）、莫米松（0.1%）或氯倍他索-17-丁酸酯（0.05%）预处理皮肤的渗透增加了3.6倍（吡美莫司，作为1%乳膏施用）和1.7倍（他克莫司，作为0.1%软膏施用）。在正常猪皮肤中，他克莫司的渗透速率比吡美莫司高11.2倍，在CS预处理皮肤中高3.5- 7.1倍，与CS的效力无关。目前的体外数据表明，在急性皮肤炎症患者或局部CS治疗后，与Protopic 0.1%和0.03%软膏相比，Elidel 1%乳膏的经皮吸收和全身药物暴露将更低。
The permeabilities of normal human and normal, inflamed, or corticosteroid (CS) pretreated skin of young domestic pigs for pimecrolimus and tacrolimus were compared in vitro, using Franz-type diffusion cells. The test articles were either used as 1.0% solutions or as the marketed formulations (Elidel 1% cream, Protopic 0.1%, and 0.03% ointment). In normal human skin, the permeation rate of pimecrolimus from the 1% cream was about sixfold lower than that of tacrolimus from 0.1% ointment and by a factor of 4.3 lower compared with tacrolimus from Protopic 0.03%. In pigs, sodium laurylsulfate-induced irritant contact dermatitis resulted in significantly faster skin permeation of both drugs from applied solutions. The permeation rate for pimecrolimus was lower than that for tacrolimus. Thus, at 24 h, pimecrolimus concentrations in the receptor fluid were 2.8-fold lower than the tacrolimus levels. Compared with normal porcine skin, permeation of drugs through hydrocortisone (1.0%)-, mometasone (0.1%)-, or clobetasol-17-butyrate (0.05%)-pretreated skin was increased by factors of 3.6 (pimecrolimus, applied as 1% cream) and 1.7 (tacrolimus, applied as 0.1% ointment). In normal pig skin, the permeation rate of tacrolimus was found to be 11.2 times higher than that of pimecrolimus and 3.5- to 7.1-fold higher in CS-pretreated skin, independent of the potency of the CSs. The present in vitro data suggest that in patients with acute skin inflammation or after therapy with topical CSs, percutaneous absorption and, as a consequence, systemic drug exposure will be lower with Elidel 1% cream as compared with Protopic 0.1% and 0.03% ointment.