Lau D T, Sharkey J W, Petryk L, Mancuso F A, Yu Z, Tse F L
Drug Metabolism and Pharmacokinetics Department, Sandoz Research Institute, Sandoz Pharmaceuticals Corporation, East Hanover, New Jersey 07936.
Pharm Res. 1994 Dec;11(12):1742-6. doi: 10.1023/a:1018963300092.
The effect of current magnitude and drug concentration on transdermal iontophoretic delivery of octreotide acetate (Sandostatin) 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 microA/cm2 to 150 microA/cm2 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 microA/cm2 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%.
