Spontaneous and forced cutaneous absorption of indomethacin in pigs and humans.

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.