Platelet‐derived endothelial cell growth factor Pharmacokinetics, organ distribution and degradation after intravenous administration in rats

Abstract

Platelet‐derived endothelial cell growth factor (PD‐ECGF) stimulates chemotaxis of endothelial cells in vitro and has angiogenic activity in vivo. Recently PD‐ECGF was shown to have thymidine phosphorylase activity. In order to study possible therapeutic applications of PD‐ECGF we used a rat model to determine its pharmacokinetics and tissue distribution after intravenous injection. [¹²⁵I]PD‐ECGF disappeared from the plasma in a biphasic manner, with estimated distribution and elimination half‐lives of 17 min and 7 h, respectively. PD‐ECGF was metabolized in the liver, excreted via the bile, and not accumulated in any organ system. The stability and long half‐life in the circulation, together with the specificity for endothelial cells, suggest that PD‐ECGF may be useful as a therapeutic agent to stimulate re‐endothelialization in vivo, or, in view of its thymidine phosphorylase activity, in chemotherapy, by decreasing the pool of available thymidine.