TRANSDERMAL IONTOPHORETIC DELIVERY OF [H-3]GHRP IN RATS

In this study, we demonstrate transdermal iontophoretic delivery of ra diolabeled growth hormone-releasing peptide ([H-3]GHRP, [H-3]SK&F 1106 79) from an iontophoretic patch delivery device in rats. [H-3]SK&F 110 679 was adsorbed on a hydrophilic microporous membrane, which was posi tioned 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). Curre nt-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 ads orbed on the membrane. Blood levels of [H-3]SK&F 110679 equivalents pe rsisted for at least 2 h after the current was turned off, indicative of depot formation in the skin. Fractions of bile and urine were analy zed by reversed-phase high-performance liquid chromatography (HPLC). T he radiochemical profiles were dominated by a single species, coelutin g 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 th e patch device, therapeutic levels of SK&F 110679 in man may be attain able by transdermal iontophoresis. (C) 1997 Elsevier Science B.V.