EFFECT OF CURRENT MAGNITUDE AND DRUG CONCENTRATION ON IONTOPHORETIC DELIVERY OF OCTREOTIDE ACETATE (SANDOSTATIN(R)) IN THE RABBIT

The effect of current magnitude and drug concentration on transdermal iontophoretic delivery of octreotide acetate (Sandostatin(R)) was examined in the rabbit. Plasma samples were collected over 24 hours and octreotide concentrations were determined by a radioimmunoassay. Without an electrical current, negligible plasma concentrations of octreotide were obtained. Following initiation of iontophoresis, plasma concentrations of octreotide increased rapidly, although did not sustain at a plateau level during the dosing period. Octreotide concentrations declined rapidly after removal of the device. Increasing the electrical current from 50 mu A/cm(2) to 150 mu A/cm(2) yielded a proportional increase in the delivery. Increasing the drug concentration in the device from 2.5 mg/mL to 5 mg/mL resulted in approximately proportional increase in plasma octreotide concentrations; however, further increase in plasma concentrations was not observed for drug concentrations beyond 5 mg/mL. Iontophoretic delivery at the conditions which yielded the highest octreotide concentrations in this study (5 mg/mL solution at 150 mu A/cm(2) for 8 hours) yielded an apparent bioavailability (which represents an underestimate of the absolute bioavailability determined when the patches are run to exhaustion) of approximately 8%.