title: Disposition of growth hormone-releasing peptide (SK&F 110679) in rat and dog following intravenous or subcutaneous administration.
abstract: 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 [3H]SK&F 110679 was assessed in bile duct-exteriorized rats from which radiolabeled biliary and urinary excreta were quantified and characterized. [3H]SK&F 110679 was excreted, predominantly in the bile, and to a large extent as intact peptide following either iv or sc administration. Although the extent of biliary excretion of radiolabel was similar following iv or sc administration (60-70% of the dose), the rate was significantly higher following iv administration. Using a specific plasma HPLC/fluorescence assay, the iv and sc pharmacokinetics of SK&F 110679 were investigated in both species. Following iv bolus administration, biphasic plasma concentration-time 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). High sc bioavailability (89-103%) was observed in both species; an apparent terminal half-life of 1 hr likely reflected slow absorption from the injection site.
authors.affiliation: SmithKline Beecham Pharmaceuticals, Drug Metabolism and Pharmacokinetics, King of Prussia, PA 19406.
authors.forename: C B
authors.initials: CB
authors.lastname: Davis
authors.forename: C S
authors.initials: CS
authors.lastname: Crysler
authors.forename: V K
authors.initials: VK
authors.lastname: Boppana
authors.forename: K L
authors.initials: KL
authors.lastname: Fong
authors.forename: G L
authors.initials: GL
authors.lastname: Joseph
authors.forename: J J
authors.initials: JJ
authors.lastname: Urbanski
authors.forename: R A
authors.initials: RA
authors.lastname: Macia
authors.forename: G R
authors.initials: GR
authors.lastname: Rhodes
mesh_terms: D000818:Animals; D001646:Bile / Q000737:chemistry; D004285:Dogs; D005260:Female; D006207:Half-Life; D007271:Injections, Intradermal; D007275:Injections, Intravenous; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D009842:Oligopeptides; C041048:growth hormone releasing hexapeptide