title: Pharmacokinetics and pharmacodynamics of growth hormone in patients on chronic haemodialysis compared with matched healthy subjects: an open, nonrandomized, parallel-group trial.
abstract: BACKGROUND
  GH may be beneficial in treating patients with end-stage renal disease (ESRD). However, the efficacy and safety of GH could be compromised by the potential for accumulation in the circulation.
  
  
  OBJECTIVE
  The objective was to investigate the pharmacokinetics and safety of GH treatment in ESRD patients.
  
  
  METHODS
  This was an open, nonrandomized, single-centre parallel-group study lasting 8-9 days.
  
  
  METHODS
  Eleven adult ESRD patients and 10 matched healthy individuals received recombinant human GH (50 microg/kg/day for 7 days) by subcutaneous injection; there were two dose reductions (25%) from Day 5/7. ESRD patients underwent dialysis four times.
  
  
  METHODS
  Serum concentrations of GH, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-I (IGFBP-I), IGFBP-III and GHBP were measured. The primary end-point was GH exposure [area-under-the-curve (AUC) calculated from the 24-h profile] on Days 7-8.
  
  
  RESULTS
  GH AUC(0-24 h) was greater for patients (387.91 +/- 134.13 microg h/l) than healthy subjects (225.35 +/- 59.63 microg h/l) and the 90% confidence interval (CI) for the estimated patient : healthy subject ratio (1.40-2.07) was not within the acceptance interval (0.67-1.50). GH AUC(18-24 h) for patients and healthy subjects (3.03 +/- 2.71 microg h/l and 6.37 +/- 4.21 microg h/l) returned approximately to baseline (2.86 +/- 3.91 microg h/l and 1.09 +/- 1.43 microg h/l); terminal half-life (t(1/2,z)) was shorter for patients (2.28 +/- 00.43 h vs. 3.23 +/- 00.75 h). No major safety issues were identified.
  
  
  CONCLUSIONS
  Results demonstrate a difference between patients and healthy subjects regarding GH AUC(0-24 h). However, GH concentrations for both groups were comparable to baseline by 20-22 h, thus GH was not retained in the circulation of ESRD patients.
authors.affiliation: Department of Clinical Pharmacology, Novo Nordisk A/S, Bagsvaerd, Denmark.
authors.forename: Irene H
authors.initials: IH
authors.lastname: Langbakke
authors.forename: Jakob N
authors.initials: JN
authors.lastname: Nielsen
authors.forename: Mia P
authors.initials: MP
authors.lastname: Skettrup
authors.forename: Angela
authors.initials: A
authors.lastname: Harper
authors.forename: Thomas
authors.initials: T
authors.lastname: Klitgaard
authors.forename: Angelika
authors.initials: A
authors.lastname: Weil
authors.forename: Eva
authors.initials: E
authors.lastname: Engelhardt
authors.forename: Martin
authors.initials: M
authors.lastname: Lange
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D002352:Carrier Proteins / Q000097:blood; D016022:Case-Control Studies; D004334:Drug Administration Schedule; D013006:Growth Hormone / Q000097:blood; D019382:Human Growth Hormone / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007279:Injections, Subcutaneous; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008875:Middle Aged; D006435:Renal Dialysis; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone; C051815:somatotropin-binding protein