洛萘帕林在银屑病皮肤中的经皮吸收与代谢
Percutaneous absorption and metabolism of lonapalene in psoriatic skin.
作者信息
Lehman P A, Tomlinson R V, Johnson J I, Olerud J E, Akers W A, Franz T J
机构信息
Division of Dermatology, School of Medicine, University of Washington, Seattle 98115.
出版信息
Pharm Res. 1992 Sep;9(9):1145-51. doi: 10.1023/a:1015843503746.
The percutaneous absorption and metabolism of lonapalene (6-chloro-2,3-dimethoxynaphthalene-1,4-diol-diacetate; RS-43179), a topically effective 5-lipoxygenase inhibitor, has been measured in six subjects with stable plaque-type psoriasis of the lower extremities. Lonapalene readily penetrates psoriatic skin, is rapidly and completely metabolized, and is almost entirely excreted in the urine. Unexpectedly we observed a trend for thigh (T) plaque skin to be more permeable than lower leg (LL) plaque skin as measured by total absorption (T, 44.8 +/- 13.4%; LL, 24.9 +/- 12.6% applied dose excreted), peak plasma levels (T, 209 +/- 107; LL, 146 +/- 81 ng Eq/ml), and peak rate of urinary excretion (T, 591.7 +/- 112.2; LL, 318.4 +/- 143.9 micrograms Eq/hr). There were also differences in the metabolic profiles between the two sites as measured by the quantity and proportion of dealkylated and conjugated products excreted in the urine.
在6名患有下肢稳定斑块型银屑病的受试者中，测定了局部有效的5-脂氧合酶抑制剂洛那帕林（6-氯-2,3-二甲氧基萘-1,4-二醇二乙酸酯；RS-43179）的经皮吸收和代谢情况。洛那帕林很容易穿透银屑病皮肤，迅速且完全代谢，几乎全部经尿液排出。出乎意料的是，我们观察到，通过总吸收量（大腿，44.8±13.4%；小腿，24.9±12.6%的给药剂量经尿液排出）、血浆峰值水平（大腿，209±107；小腿，146±81 ng Eq/ml）和尿排泄峰值速率（大腿，591.7±112.2；小腿，318.4±143.9微克Eq/小时）来衡量，大腿（T）斑块皮肤比小腿（LL）斑块皮肤的渗透性更高。通过尿液中排出的脱烷基化产物和结合产物的数量和比例来衡量，两个部位的代谢谱也存在差异。
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