Iontophoresis driven concentrations of topically administered diclofenac in skeletal muscle and blood of healthy subjects

The present open single-centre, descriptive and comparative pharmacokinetic study aimed to investigate the efficacy of iontophoresis to enhance transdermal delivery by measuring concentration vs. time profiles of diclofenac in local tissue and in plasma in two separate study periods. Period 1 determined diclofenac concentrations in both calf muscles simultaneously by using microdialysis after applying diclofenac gel topically as a single dose of 5 g with or without iontophoresis in eight healthy volunteers. In period 2, the same dose was applied to another 8 volunteers to determine plasma concentrations of diclofenac either with or without iontophoresis in a cross over design. In period 1, tissue concentrations were found to be under the limit of detection of 0.5 ng/ml both with and without iontophoresis in all subjects. In period 2, after iontophoresis in 75 % of study participants, plasma concentrations of diclofenac could be determined, but only in 25 % without iontophoresis. Although area under the concentration-time-curve (AUC, 187.97 +/- 315.92 vs. 22.92 +/- 42.44 ng*min/ml) and maximum concentration (C-max, 2.06 +/- 3.79 vs. 0.22 +/- 0.41 ng/ml) values showed a numerically clear trend for higher values with iontophoresis compared to passive diffusion, no significant difference could be found due to high inter-individual variability. In total, 18.75 % of all subjects presented adverse events. Despite a higher percentage of subjects showed detectable plasma levels of diclofenac after iontophoresis, iontophoresis failed to achieve potentially more effective topical concentrations. The typical mechanism of iontophoresis like electromigration, electroosmosis and increased subcutaneous circulation could be responsible for the results of the present observation. Additional clinical studies are needed to justify the transdermal delivery of diclofenac by using iontophoresis.