Murakami T, Yoshioka M, Yumoto R, Higashi Y, Shigeki S, Ikuta Y, Yata N
Department of Biopharmaceutics, Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Japan.
J Pharm Pharmacol. 1998 Jan;50(1):49-54. doi: 10.1111/j.2042-7158.1998.tb03304.x.
Topical delivery of tranilast (N-(3,4-dimethoxycinnamoyl)anthranic acid), an inhibitor of collagen synthesis and a therapeutic drug for keloid and hypertrophic scar, was examined, in rats, with oleic acid alone or a combination of oleic acid and propylene glycol as penetration enhancer. Evaluation was by measurement of the concentration of tranilast in plasma and in the dialysate from skin microdialysis. When tranilast at a dose of 1.5 mg was applied topically as an ethanol solution containing 5% polyvinylpyrrolidone on a dorsal skin surface (2.25 cm2), the maximum concentration of tranilast in skin dialysate was approximately 2 microM. When 10 or 20% oleic acid was added to the same ethanol solution the maximum concentration of tranilast in the dialysate increased to 10-20 microM, and this value was further increased to 60 microM by the addition of a combination of oleic acid (10 or 20%) and propylene glycol (10%) to the solution. With the combination of oleic acid and propylene glycol the area under the plot of the concentration of tranilast in skin dialysate against time between 0 and 4 h (AUC0-4) was more than 400-fold that after intravenous administration. The transdermal bioavailability of tranilast as assessed by the AUC0-4 of tranilast in plasma, was 0.2% of the dose applied in the ethanol solution, 3-5% of that applied in the ethanol solution containing oleic acid, and 14-16% of that applied in the ethanol solution containing both oleic acid and propylene glycol. These results suggest that the topical delivery of tranilast with an absorption enhancer such as a mixture of oleic acid and propylene glycol might be a more effective medication than oral administration of tranilast for the treatment of keloid and hypertrophic scar.
曲尼司特（N-(3,4-二甲氧基肉桂酰)邻氨基苯甲酸）是一种胶原蛋白合成抑制剂，也是治疗瘢痕疙瘩和增生性瘢痕的药物。本研究在大鼠中考察了单独使用油酸或联合使用油酸与丙二醇作为渗透促进剂时曲尼司特的局部给药情况。通过测量血浆和皮肤微透析透析液中曲尼司特的浓度进行评估。当以含5%聚乙烯吡咯烷酮的乙醇溶液形式在大鼠背部皮肤表面（2.25 cm²）局部应用1.5 mg曲尼司特时，皮肤透析液中曲尼司特的最大浓度约为2 μM。当在同一乙醇溶液中添加10%或20%油酸时，透析液中曲尼司特的最大浓度增加至10 - 20 μM，通过在溶液中添加10%或20%油酸与10%丙二醇的组合，该值进一步增加至60 μM。使用油酸和丙二醇的组合时，皮肤透析液中曲尼司特浓度随时间变化曲线在0至4小时的曲线下面积（AUC0 - 4）比静脉给药后高400多倍。以血浆中曲尼司特的AUC0 - 4评估，曲尼司特的经皮生物利用度在乙醇溶液中给药时为给药剂量的0.2%，在含油酸的乙醇溶液中给药时为3 - 5%，在含油酸和丙二醇的乙醇溶液中给药时为14 - 16%。这些结果表明，对于瘢痕疙瘩和增生性瘢痕的治疗，使用油酸和丙二醇混合物等吸收促进剂进行曲尼司特的局部给药可能比口服给药更有效。
