Dtw. Lau et al., EFFECT OF CURRENT MAGNITUDE AND DRUG CONCENTRATION ON IONTOPHORETIC DELIVERY OF OCTREOTIDE ACETATE (SANDOSTATIN(R)) IN THE RABBIT, Pharmaceutical research, 11(12), 1994, pp. 1742-1746
The effect of current magnitude and drug concentration on transdermal
iontophoretic delivery of octreotide acetate (Sandostatin(R)) was exam
ined in the rabbit. Plasma samples were collected over 24 hours and oc
treotide concentrations were determined by a radioimmunoassay. Without
an electrical current, negligible plasma concentrations of octreotide
were obtained. Following initiation of iontophoresis, plasma concentr
ations of octreotide increased rapidly, although did not sustain at a
plateau level during the dosing period. Octreotide concentrations decl
ined rapidly after removal of the device. Increasing the electrical cu
rrent from 50 mu A/cm(2) to 150 mu A/cm(2) yielded a proportional incr
ease in the delivery. Increasing the drug concentration in the device
from 2.5 mg/mL to 5 mg/mL resulted in approximately proportional incre
ase 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 hi
ghest octreotide concentrations in this study (5 mg/mL solution at 150
mu A/cm(2) for 8 hours) yielded an apparent bioavailability (which re
presents an underestimate of the absolute bioavailability determined w
hen the patches are run to exhaustion) of approximately 8%.