Studies on disposition of tacrolimus after topical application using several experimental models including a new hybrid skin-model

在这项研究中，我研究了局部应用后影响他克莫司处置的因素，使用了几个实验模型，包括一个新的杂交皮肤模型。无毛大鼠模型和新型杂交皮肤模型均显示他克莫司全身吸收依赖于角质层屏障功能。经表皮水分流失（TEWL）与他克莫司的全身吸收有关，初步测定TEWL有助于避免全身副作用。在炎症皮肤中，虽然他克莫司与真皮层溶出的血浆蛋白结合导致吸收延迟，但炎症皮肤的血流量和血管通透性增加可能与后期他克莫司血药浓度高有关。本研究结果可用于他克莫司软膏治疗特应性皮炎的安全用药。

In this study, I examined factors affecting disposition of tacrolimus after topical application using several experimental models including a new hybrid skin-model. Systemic absorption of tacrolimus depended on the barrier function of stratum corneum was shown in hairless rat model and the new hybrid skin-model. Trans Epidermal Water Loss (TEWL) was correlated with the systemic absorption of tacrolimus and it was suggested that preliminary determination of TEWL is useful to avoid the systemic side effect. In inflamed skin, although delayed absorption was caused by tacrolimus binding to leaching plasma proteins in the dermis, increased blood flow and blood vessel permeability in the inflamed skin can be related with high blood concentration of tacrolimus in the later phase. The results obtained in this study can be applicable for safe medication of atopic dermatitis using tacrolimus ointment.