Percutaneous absorption of vanilloids: In vivo and in vitro studies
Percutaneous absorption of vanilloids: In vivo and in vitro studies
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DOI：
10.1021/js950484a
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发表时间：
1997-01-01
影响因子：
3.8
通讯作者：
Kinnett, GO
中科院分区：
文献类型：
--
作者：
Kasting, GB;Francis, WR;Kinnett, GO
辣椒素的三种高度亲脂性类似物-香草基壬酰胺（VN）、奥香草和NE-21610-的经皮吸收在CD：VAF大鼠体内以及通过离体CD：VAF和SkH：Fz大鼠皮肤和人尸体皮肤在体外进行测量。通过放射性标记技术监测吸收和皮肤代谢。所有种属中渗透性的等级顺序为VN >奥瓦尼> NE-21610，与它们的物理性质预期一致，大鼠皮肤比人皮肤渗透性高，VN的渗透系数范围为4至8，奥瓦尼为10至20，NE-21610约为10至100。所有三种化合物在通过新鲜SkH：Fz大鼠皮肤期间均被广泛代谢，其中至少两种化合物的主要降解途径涉及酰胺键水解（未鉴别NE-21610的代谢物）。对于体外研究，采用一系列受体溶液来确定最佳模拟体内吸收的一组条件。含防腐剂和1-6%聚氧乙烯-20油基醚（Oleth-20）的磷酸盐缓冲盐水的结果与给药后24 h内所有三种化合物的体内结果一致;此后，体内吸收率下降，但体外吸收率保持相对恒定。缓冲盐水或含0.5%牛血清白蛋白的盐水导致奥瓦尼和NE-21610的体内渗透率明显低估，而1：1乙醇：水溶液导致所有三种化合物的体内吸收率总体高估。
The percutaneous absorption of three highly lipophilic analogs of capsaicin-vanillylnonanamide (VN), olvanil, and NE-21610-was measured in vivo in the CD:VAF rat, and in vitro through excised CD:VAF and SkH:Fz rat skin and human cadaver skin. Absorption and skin metabolism were monitored by radiolabel techniques. The rank order of penetration in all species was VN > olvanil > NE-21610, in accordance with that expected from their physical properties, Rat skin was more permeable than human skin by factors ranging from 4 to 8 for VN, 10 to 20 for olvanil, and approximate to 10 to 100 for NE-21610. All three compounds were extensively metabolized during passage through fresh SkH:Fz rat skin, with the primary route of degradation for at least two of the compounds involving hydrolysis of the amide bond (the metabolites of NE-21610 were not identified). For the in vitro studies a range of receptor solutions was employed to determine a set of conditions that best mimicked in vivo absorption. The results with phosphate-buffered saline containing a preservative and 1-6% polyoxyethylene-20 oleyl ether (Oleth-20) were in good agreement with in vivo results for all three compounds for periods up to 24 h post-dose; after this time, in who absorption rates declined but in vitro rates remained relatively constant. Buffered saline or saline containing 0.5% bovine serum albumin led to marked underestimates of in vivo penetration for olvanil and NE-21610, whereas a 1:1 ethanol: water solution led to gross overestimates of the in viva absorption rates for all three compounds.