title: Pharmacokinetics and distribution of heparin-binding growth factor I (endothelial cell growth factor) in the rat.
abstract: Heparin-binding growth factor I (HBGF I), previously designated as endothelial cell growth factor, is a potent mitogen for endothelial cells in vitro, which may prove useful for promoting endothelial regeneration in vivo. Analysis of the pharmacokinetics and organ distribution of HBGF I is necessary before use of HBGF I as a pharmacological agent. Consequently, pharmacological studies were carried out with [125I]HBGF I in the rat. Intravenous injections of HBGF I were given with or without heparin (2.5 units/ng HBGF I). Blood concentrations of HBGF I decreased by one half 17 seconds after HBGF I bolus. This time was prolonged to 60 seconds when HBGF I was injected with heparin. The elimination half-life of HBGF I was 14 minutes in the presence of heparin. The highest concentrations of HBGF I following intravenous bolus were found in kidney, liver, and spleen, and the lowest in fat and brain. Heparin increased HBGF I concentrations in blood and all organs measured except kidney, which was significantly decreased (p less than 0.01). Intact HBGF I was recoverable from blood 5 minutes following intravenous administration. HBGF I underwent near-complete proteolytic digestion after more prolonged ex vivo incubation with rat plasma, but HBGF I was protected from proteolysis when incubations were conducted in the presence of heparin. Thus, it is feasible that HBGF I can be administered as a pharmacological agent in the presence of heparin. Further studies assessing acceleration of in vivo endothelial growth using HBGF I with heparin appear warranted.
authors: Surgery Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892.
authors: T K
authors: TK
authors: Rosengart
authors: J P
authors: JP
authors: Kuperschmid
authors: T
authors: T
authors: Maciag
authors: R E
authors: RE
authors: Clark
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D016220:Fibroblast Growth Factor 1; D005720:Gamma Rays; D006133:Growth Substances / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D006493:Heparin / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D011859:Radiography; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D006133:Growth Substances; D007457:Iodine Radioisotopes; D008934:Mitogens; D016220:Fibroblast Growth Factor 1; D006493:Heparin