DISPOSITION OF GROWTH HORMONE-RELEASING PEPTIDE (SK-AND-F-110679) IN RAT AND DOG FOLLOWING INTRAVENOUS OR SUBCUTANEOUS ADMINISTRATION

The disposition of growth hormone releasing peptide (SK&F 110679) has been studied in male Sprague-Dawley rats and in male and female beagle dogs following intravenous (iv) and subcutaneous (sc) administration. Mass balance/excretion of [H-3]SK&F 110679 was assessed in bile duct- exteriorized rats from which radiolabeled biliary and urinary excreta were quantified and characterized. [H-3]SK&F 110679 was excreted, pred ominantly in the bile, and to a large extent as intact peptide followi ng either iv or sc administration. Although the extent of biliary excr etion of radiolabel was similar following iv or sc administration (60- 70% of the dose), the rate was significantly higher following iv admin istration. Using a specific plasma HPLC/ fluorescence assay, the iv an d sc pharmacokinetics of SK&F 110679 were investigated in both species . Following iv bolus administration, biphasic plasma concentration-tim e profiles were observed, and the initial phases were characterized by 2-4 min half-lives. Systemic plasma clearance was 27 ml/min/kg in the rat (0.4 mg/kg dose) and 17 ml/min/kg in the dog (0.5 mg/kg dose). Hi gh sc bioavailability (89-103%) was observed in both species; an appar ent terminal half life of 1 hr likely reflected slow absorption from t he injection site.