Objective: This study was performed to determine the pharmakocinetics of recombinant leptin in lean rats and to test the hypothesis that the kidneys play an important role in the clearance of leptin from the circulation.
Design: 126I-leptin was administered by bolus intravenous injection. Blood samples were taken at various time points ranging from 1-180 min after administration and assayed for leptin. Pharmacokinetic parameters were determined in normal animals and after either bilateral nephrectomy or bilateral ureteral ligation.
Results: Leptin was eliminated from the circulation following a three compartment model. The importance of the kidneys to the systemic clearance of leptin was studied by administrating leptin to binephrectomized rats. The systemic clearance of leptin in anephric rats was only 19% of that calculated for control animals. In order to assess the role of glomerular filtration, both ureters were ligated 5 h before leptin administration. Ureteral ligation reduced the systemic clearance of leptin by 30%.
Conclusion: These findings demonstrate that the short half life of leptin in the circulation is mainly determined by efficient renal clearance which is mediated in part by glomerular filtration.