肾脏在大鼠生长激素（rhGH）的清除过程中起核心作用。

The kidneys play a central role in the clearance of rhGH in rats.

作者信息

Vestergaard Bill, Thygesen Peter, Kreilgaard Mads, Fels Johannes Josef, Lykkesfeldt Jens, Agersø Henrik

机构信息

Global Research, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Måløv, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, DK-1870 Frederiksberg C, Denmark.

Global Research, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Måløv, Denmark.

出版信息

Eur J Pharm Sci. 2016 Apr 30;86:29-33. doi: 10.1016/j.ejps.2016.02.019. Epub 2016 Mar 2.

DOI:10.1016/j.ejps.2016.02.019

PMID:26946443

Abstract

The kidneys are thought to play an important role in the clearance of recombinant human growth hormone (rhGH), but the relative importance is not clear. Obtaining knowledge of clearance pathway is an important prerequisite for the development of new long acting growth hormone analogues targeted at treatment of patients with growth hormone disorders. The purpose of this study was to investigate the relative importance of the kidneys in the clearance of rhGH. The study employed a newly validated nephrectomy rat model and a population based pharmacokinetic approach to assess renal clearance of rhGH in non-anesthetized rats, anesthetized rats and in nephrectomized anesthetized rats. Clearance in non-anesthetized rats was 290 ml/h/kg. This was reduced to 185 ml/h/kg by anesthesia and further reduced to 18 ml/h/kg by nephrectomy. As nephrectomy was able to reduce clearance with 90%, we conclude that renal clearance plays a pivotal role in the elimination of rhGH in rats.

摘要

肾脏被认为在重组人生长激素（rhGH）的清除过程中发挥重要作用，但其相对重要性尚不清楚。了解清除途径是开发针对生长激素紊乱患者治疗的新型长效生长激素类似物的重要前提。本研究的目的是调查肾脏在rhGH清除中的相对重要性。该研究采用了一种新验证的肾切除术大鼠模型和基于群体的药代动力学方法，以评估未麻醉大鼠、麻醉大鼠和肾切除麻醉大鼠中rhGH的肾清除率。未麻醉大鼠的清除率为290 ml/h/kg。麻醉后降至185 ml/h/kg，肾切除后进一步降至18 ml/h/kg。由于肾切除能够将清除率降低90%，我们得出结论，肾清除在大鼠rhGH的消除中起关键作用。