title: The kidneys play a central role in the clearance of rhGH in rats.
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.
authors.affiliation: 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. Electronic address: blve@novonordisk.com.
authors.forename: Bill
authors.initials: B
authors.lastname: Vestergaard
authors.affiliation: Global Research, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Måløv, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Thygesen
authors.affiliation: Global Research, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Måløv, Denmark.
authors.forename: Mads
authors.initials: M
authors.lastname: Kreilgaard
authors.affiliation: Global Research, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Måløv, Denmark.
authors.forename: Johannes Josef
authors.initials: JJ
authors.lastname: Fels
authors.affiliation: Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, DK-1870 Frederiksberg C, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Lykkesfeldt
authors.affiliation: Global Research, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Måløv, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Agersø
mesh_terms: D000818:Animals; D019382:Human Growth Hormone / Q000097:blood / Q000493:pharmacokinetics*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009392:Nephrectomy; D017207:Rats, Sprague-Dawley
chemical_list: D019382:Human Growth Hormone
keywords: Clearance; Kidney; Nephrectomy; Non-linear mixed effect modeling; Pharmacokinetics; rhGH