Disposition of growth hormone-releasing peptide (SK&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 [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.
Davis
C B
CB
SmithKline Beecham Pharmaceuticals, Drug Metabolism and Pharmacokinetics, King of Prussia, PA 19406.
Crysler
C S
CS
Boppana
V K
VK
Fong
K L
KL
Joseph
G L
GL
Urbanski
J J
JJ
Macia
R A
RA
Rhodes
G R
GR
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
D009842:Oligopeptides; C041048:growth hormone releasing hexapeptide