薄荷醇和氮酮对吲哚美辛体外促透作用的比较

Comparison of the effect of azone and menthol on the percutaneous absorption of indomethacin in vitro

目的 :以吲哚美辛为模型药物 ,对薄荷醇和氮酮的促透特性进行比较 ,并探讨两种促透剂合用时的促透效果。方法 :在离体透皮实验装置上进行透皮试验 ,由浓度计算累计透过量、透皮速率、稳态流量、滞后时间等指标。结果 :用促透剂后 ,吲哚美辛的透皮速率均极显著增加 ,分别比对照组增加6 .2 1、4 .91和 6 .92倍 ;当两种促透剂联合应用时 ,透皮速率比单独应用时显著增加 (P <0 .0 1)。促透剂可使吲哚美辛透皮吸收的时滞均明显缩短 ;薄荷醇组对时滞的缩短作用比薄荷醇和氮酮联用组更为显著 (P <0 .0 1)。对吲哚美辛透皮吸收稳态流量的影响 ,氮酮单独应用不明显 ,而薄荷醇则表现为降低作用 ;但当两种促透剂联合应用时 ,则表现为明显的增强效应 ,比单独应用时分别增加 2 .78和 1.38倍。结论 :薄荷醇和氮酮对吲哚美辛的体外经皮吸收具有显著的促进作用 。

AIM: To compare the permeation enhancing characters of menthol and azone on the model drug of indomethacin and to study the enhancing effect when the two agents were used in combination. METHODS: The transdermal test was conduced on the penetration experiment apparatus of isolated skin. The cumulate penetrated amount, penetrating rate, stable flux and lag time were calculated upon the concentrations. RESULTS: After adding the penetration enhancer, the penetrating rate of indomethacin increased remarkably. It was 6.21 , 4.91 and 6.92 times of that of the controls respectively. When used in combination, the two penetration enhancers increased much more the penetrating rate than being used separately (P< 0.01 ). The penetration enhancer could shorten the lag time of absorption of indomethacin evidently. The lag time in the menthol group was shortened more evidently than that in the combined group (P< 0.01 ). Azone had little effect on the stable flux of absorption of indomethacin, while menthol decreased it. When the two penetration enhancers were used in combination, distinct enhancing effect was observed. It was 2.78 and 1.38 times of that of separate agents respectively. CONCLUSIONS: Menthol and azone can remarkably enhance the percutaneous absorption of indomethacin in vitro, and the enhancing effect is strongened when they are used in combination.