INVIVO TRANSDERMAL IONTOPHORETIC DELIVERY OF GROWTH-HORMONE RELEASING-FACTOR GRF (1-44) IN HAIRLESS GUINEA-PIGS

The present study was undertaken to determine the effect of iontophoresis on the transdermal delivery of growth hormone releasing factor (GRF 1-44), a peptide shown to be effective in promoting linear growth in short-statured children. A reservoir patch with a conductive peptide gel was used for this purpose and the delivery of the peptide was monitored in vivo in hairless guinea pigs using a pulsed voltage generator specifically designed to provide a current limit. The current limit selected for the present study was 0.17 mA/cm2 at 50 KHz and 50% duty cycle. The current conditions were selected based on previously performed in vitro experiments. The half life, volume of distribution and area under the curve (AUC) were determined to be 0.389 h, 8.861 and 0.453 (mg/ml) h, respectively from an intravenous administration of a 10-mu-g/kg dose in the same species. Using this information, a flux of 3.16-mu-g/h was calculated based on a steady-state plasma concentration of about 0.20 ng/ml. This steady-state level was similar to a peak plasma level achieved after a subcutaneous dose of 10-mu-g/kg. An in vivo animal model, fabrication of a patch system and design of a unique pulsed voltage generator with current limiting feature have been shown, which can be used to determine the iontophoretic delivery of compounds of interest.