Cumin F, Baum H P, Levens N
Ciba-Geigy Ltd., Basel, Switzerland.
Int J Obes Relat Metab Disord. 1996 Dec;20(12):1120-6.
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.
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.
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%.
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.
本研究旨在确定重组瘦素在瘦大鼠体内的药代动力学，并验证肾脏在清除循环中瘦素过程中起重要作用这一假说。
通过静脉推注给予126I-瘦素。在给药后1至180分钟的不同时间点采集血样并检测瘦素。在正常动物以及双侧肾切除或双侧输尿管结扎后测定药代动力学参数。
瘦素按照三室模型从循环中消除。通过给双侧肾切除的大鼠注射瘦素，研究了肾脏对瘦素全身清除的重要性。无肾大鼠体内瘦素的全身清除率仅为对照动物计算值的19%。为了评估肾小球滤过的作用，在注射瘦素前5小时结扎双侧输尿管。输尿管结扎使瘦素的全身清除率降低了30%。
这些发现表明，瘦素在循环中的短半衰期主要由高效的肾脏清除决定，而肾脏清除部分由肾小球滤过介导。
