Transdermal Iontophoretic Delivery of [3H]GHRP in Rats

In this study, we demonstrate transdermal iontophoretic delivery of radiolabeled growth hormone-releasing peptide ([H-3]GHRP, [H-3]SK&F 110679) from an iontophoretic patch delivery device in rats. [H-3]SK&F 110679 was adsorbed on a hydrophilic microporous membrane, which was positioned on a support in the device and sealed in place. A silver/silver chloride electrode system was used for iontophoresis and a potential of 4.5 V (rectangular pulse, 40 kHz, 30% duty cycle) was applied using an Advance depolarizing pulse iontophoresis system (ADIS-4030). Current-dependent appearance of [H-3]SK&F 110679 equivalents in blood, bile and urine did not depend on membrane loading between 1.8 and 8 mg adsorbed on the membrane. Blood levels of [H-3]SK&F 110679 equivalents persisted for at least 2 h after the current was turned off, indicative of depot formation in the skin. Fractions of bile and urine were analyzed by reversed-phase high-performance liquid chromatography (HPLC). The radiochemical profiles were dominated by a single species, coeluting with intact [H-3]SK&F 110679. A flux of at least 0.8-1.2 ug/h per cm(2) was achieved, indicating that, with appropriate optimization of the patch device, therapeutic levels of SK&F 110679 in man may be attainable by transdermal iontophoresis. (C) 1997 Elsevier Science B.V.