Pharmacokinetics and pharmacodynamics of growth hormone in patients on chronic haemodialysis compared with matched healthy subjects: an open, nonrandomized, parallel-group trial.
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.
Langbakke
Irene H
IH
Department of Clinical Pharmacology, Novo Nordisk A/S, Bagsvaerd, Denmark.
Nielsen
Jakob N
JN
Skettrup
Mia P
MP
Harper
Angela
A
Klitgaard
Thomas
T
Weil
Angelika
A
Engelhardt
Eva
E
Lange
Martin
M
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
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