Iontophoretic Delivery in Rat

ABSTRACT: The percutaneous penetration of flurbiprofen delivered by iontophoresis was investigated in the hairless rat. Unbound concentrations of flurbiprofen in dermis and subcutaneous tissue were continuously measured by on-line microdialysis. Simulta-neously, a conventional blood sampling was performed. Linear microdialysis probes were implanted in dermis and in subcutaneous tissue at a depth of 398.3 15.3 and 1878 35.8 mm, respectively. Commercial patches were used to deliver flurbiprofen for 15minat a current density of 0.4mA/cm2. Invivo recoveries of bothprobes, determinedby using naproxen as retrodialysis calibrator, were 26.0 0.3 and 72.9 0.7 % for dermal and subcutaneous probe, respectively. After iontophoretic delivery, a gradient in mean tissue unbound concentrations was observed, with a Cmax in dermis of 8.7 0.4 mg/mL as compared with subcutaneous Cmax of 0.5 0.1 mg/mL. The area under the unbound concentration curve in dermis was 13-fold higher than that in the subcutaneous tissue. Total plasma concentration curves showeda rapid absorption phasewith aTmax of 30min andCmax of 1.8 0.1 mg/mL. In conclusion, iontophoresis deliverywas demonstrated to be efficient to deliver a high amount of flurbiprofen in dermis and underlying tissue with a fast input rate whereasmaintaining a low plasma exposure. 2004Wiley-Liss, Inc. and th