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

The systemic pharmacokinetics and local drug distribution of sodium diclofenac in skin and underlying tissues was studied. Iontophoresis facilitated local and systemic delivery of diclofenac sodium compared with passive diffusion. The maximum plasma concentration of sodium diclofenac was achieved within 1 h of iontophoresis, and the delivery was proportional to applied current density (371 +/- 141 and 132 +/- 62 microg/L at 0.5 and 0.2 mA/cm(2), respectively). The in vivo delivery efficiency for diclofenac in rabbit was 0.15 mg/mA.h. The concentrations of sodium diclofenac in the skin, subcutaneous tissue, and muscle beneath the drug application site (cathode) were significantly greater than plasma concentrations and concentrations of drug in similar tissues at the untreated sites. The results thus suggest that the cutaneous microvasculature is not always a perfect "sink" and that transdermal 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.