Pharmacokinetic and local tissue disposition of [C-14]sodium diclofenac following iontophoresis and systemic administration in rabbits

The systemic pharmacokinetics and local drug distribution of sodium diclofe nac in skin and underlying tissues was studied. Iontophoresis facilitated l ocal and systemic delivery of diclofenac sodium compared with passive diffu sion. The maximum plasma concentration of sodium diclofenac was achieved wi thin 1 h of iontophoresis, and the delivery was proportional to applied cur rent density (371 +/- 141 and 132 +/- 62 mug/L at 0.5 and 0.2 mA/cm(2) resp ectively). The in vivo delivery efficiency for diclofenac in rabbit was 0.1 5 mg/mA.h. The concentrations of sodium diclofenac in the skin, subcutanoeu s tissue, and muscle beneath the drug application site (cathode) were signi ficantly greater than plasma concentrations and concentrations of drug in s imilar tissues at the untreated sites. The results thus suggest that the cu taneous microvasculature is not always a perfect "sink" and that transderma l iontophoresis facilitated the direct penetration of diclofenac sodium to deeper tissues. No skin irritation was observed up to 0.5 mA/cm(2) current density and 7 mg/mL sodium diclofenac concentration. (C) 2001 Wiley-Liss, I nc. and the American Pharmaceutical Association.