Behrendt H, Korting H C
Department of Dermatology, University of Munich, FRG.
Skin Pharmacol. 1990;3(1):41-4. doi: 10.1159/000210839.
Amide hydrolysis of indomethacin was investigated in rabbit skin using the isolated perfused rabbit ear model. Indomethacin was applied topically on the surface area of 4 rabbit ears using a 1% alcoholic solution (Elmetacin). Indomethacin and its hydrolytic product N-deschloro-benzoyl-indomethacin (DBI) were determined in the venous efflux. The concentrations of indomethacin and DBI increased during the first 160 min and remained constant thereafter, the concentrations amounting from 0.041 +/- 0.001 to 0.497 +/- 0.018 nmol/min/cm2 (indomethacin) and from 0.84 +/- 0.03 to 3.24 +/- 0.31 pmol/min/cm2 (DBI). Thus steady state was reached with both substances, indicating a formation of DBI in the range of 0.65-2.01%. Considering the low hydrolytic turnover rate, the limited efficacy of topically applied indomethacin in the treatment of skin diseases does not seem to be due to extensive metabolic inactivation via amide hydrolysis in this target organ.
使用离体灌注兔耳模型，在兔皮肤中研究了吲哚美辛的酰胺水解。使用1%乙醇溶液（艾美辛）将吲哚美辛局部应用于4只兔耳的表面积。在静脉流出液中测定吲哚美辛及其水解产物N-去氯苯甲酰基吲哚美辛（DBI）。吲哚美辛和DBI的浓度在最初160分钟内升高，此后保持恒定，浓度范围为0.041±0.001至0.497±0.018 nmol/分钟/平方厘米（吲哚美辛）和0.84±0.03至3.24±0.31 pmol/分钟/平方厘米（DBI）。因此两种物质均达到稳态，表明DBI的生成率在0.65 - 2.01%范围内。考虑到水解周转率较低，局部应用吲哚美辛在治疗皮肤疾病方面疗效有限，似乎并非由于该靶器官中通过酰胺水解进行的广泛代谢失活所致。
