Pratzel H, Dittrich P, Kukovetz W
J Rheumatol. 1986 Dec;13(6):1122-5.
Indomethacin can permeate the normal skin of laboratory animals as well as humans, therefore, we investigated whether and what extent this process may be intensified by sonophoresis or iontophoresis. To 6 pigs Amuno-Gel (MSD Sharp & Dohme) (indocid gel) containing 1% indomethacin was applied over 5 h iontophoretically through the skin of the back, and the blood and urine concentrations were measured by high performance liquid chromatography with inline post column hydrolysis and fluorimetric detection. Nonassisted skin uptake was measured 1 to 2 weeks later in the same animals each serving as its own control. Iontophoresis (0.1 mA/cm2) increased maximum indomethacin levels from 32 (controls) to 82 ng/ml and urinary excretion over 5 h from 29.4 to 181.1 ng/cm2 of treated skin area. Sonophoresis did not improve indomethacin absorption. In 7 human volunteers, iontophoretic application of indomethacin over 1 h onto the skin of the back (1380 cm2 surface area) increased maximum plasma levels from 43 ng/ml (controls) to 221 ng/ml, and the urinary excretion over a total of 5 h from 18.1 (controls) to 97.6 ng/cm2. As calculated from the fraction of indomethacin excreted in the urine, about 0.2 microgram indomethacin/cm2 of treated skin area taken up spontaneously and about 1.0 microgram/cm2 was transported by iontophoresis.
吲哚美辛能够渗透实验动物以及人类的正常皮肤，因此，我们研究了超声导入法或离子导入法是否以及在何种程度上会增强这一过程。给6头猪通过背部皮肤进行5小时的离子导入，施加含1%吲哚美辛的Amuno - Gel（默克雪兰诺公司）（消炎痛凝胶），并采用在线柱后水解和荧光检测的高效液相色谱法测量血液和尿液浓度。1至2周后，在同一动物身上测量非辅助性皮肤摄取量，每只动物自身作为对照。离子导入（0.1 mA/cm²）使吲哚美辛的最大水平从32（对照）增至82 ng/ml，且5小时内尿液排泄量从29.4增至181.1 ng/cm²的处理皮肤面积。超声导入法未改善吲哚美辛的吸收。在7名人类志愿者中，将吲哚美辛通过离子导入法在背部皮肤（1380 cm²表面积）上施加1小时，使血浆最大水平从43 ng/ml（对照）增至221 ng/ml，且总共5小时内尿液排泄量从18.1（对照）增至97.6 ng/cm²。根据尿液中排泄的吲哚美辛比例计算，约0.2微克吲哚美辛/cm²的处理皮肤面积自发摄取，约1.0微克/cm²通过离子导入法转运。
