Plasma clearance and tissue distribution of recombinant human platelet-derived growth factor (B-chain homodimer) in...

125I-labeled human recombinant platelet-derived growth factor (B-chain homodimer; rHuPDGF-BB) was intravenously injected into male rats, and plasma clearance and tissue distribution of total and acid-insoluble radioactivity were determined. Insoluble radioactivity was rapidly cleared from plasma in a biphasic manner with estimated distribution and elimination half-lives of 5.2 and 68 min, respectively. Less than 10% of the injected radioactivity remained in plasma at 1 hr after injection. rHuPDGF-BB was widely distributed throughout body tissues. However, acid-insoluble radioactive concentrations greater than those in plasma were only observed in liver, kidneys, and spleen. The radioactive concentration of most tissues declined rapidly between 1 and 4 hr but increased in the intestinal contents. Radioactive concentrations decreased in all tissues and intestinal contents at 8 and 24 hr. Urine samples collected at the latter interval showed that 39% of the dose was excreted by the kidneys in an acid-soluble form. These results suggest that the rapid clearance of rHuPDGF-BB from plasma is the result of widespread tissue distribution, metabolism by the liver, and excretion by the kidneys. In this respect, the pharmacokinetic behavior of rHuPDGF-BB resembles that of other lymphokines and growth factors that have recently been studied.