Transdermal iontophoretic delivery of ketoprofen through human cadaver skin and in humans

Abstract

Transdermal iontophoretic delivery of ketoprofen in cadaver skin and healthy volunteers was examined. In vitro anodic and cathodic iontophoresis (0.5 mA/cm 2, 3 h) of ketoprofen (75 mg/ml) resulted in equivalent intracutaneous ketoprofen permeation (232.1 ± 27.1 vs. 275.0 ± 141.0 μg/cm 2, respectively), which in turn was higher than passive intracutaneous uptake of ketoprofen (40.7 ± 42.1 μg/cm 2). In contrast, only cathodic iontophoresis resulted in transcutaneous ketoprofen permeation across cadaver skin, under these conditions. The in vitro study was then repeated to achieve transcutaneous permeation of ketoprofen at clinical iontophoretic parameters (0.28 mA/cm 2, 40 min) by increasing drug concentration to 300 mg/ml. No stereo-selective permeation of R- and S-ketoprofen enantiomers was observed in vitro. In humans, cathodic iontophoresis of 300 mg/ml ketoprofen (0.28 mA/cm 2, 40 min) was performed at the wrist. Ketoprofen was detected at 40 min (0.88 ± 0.42 μg/ml) from the forearm veins of the ipsilateral arm. Urinary excretion of ketoprofen totaled 790 ± 170 μg at 16 h post iontophoresis. This investigation is the first to clearly demonstrate transcutaneous iontophoresis of an antiinflammatory agent in humans utilizing a commercially cleared iontophoretic device. The investigation also adds to the very limited number of publications in the area of iontophoretic delivery of drugs to humans.