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Pharmacokinetics and pharmacodynamics of growth hormone in patients on chronic haemodialysis compared with matched healthy subjects: an open, nonrandomized, parallel-group trial.

Langbakke IH, Nielsen JN, Skettrup MP, Harper A, Klitgaard T, Weil A, Engelhardt E, Lange M - Clin. Endocrinol. (Oxf) (2007)

Bottom Line: However, the efficacy and safety of GH could be compromised by the potential for accumulation in the circulation.No major safety issues were identified.Results demonstrate a difference between patients and healthy subjects regarding GH AUC(0-24 h).

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacology, Novo Nordisk A/S, Bagsvaerd, Denmark.

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.

Design: This was an open, nonrandomized, single-centre parallel-group study lasting 8-9 days.

Subjects: 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.

Measurements: 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.

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Related in: MedlinePlus

Trial design. All subjects had eight visits to the trial centre, seven daily doses of rhGH and a follow-up visit (Days 16–19). Patients had an additional assessment visit on Days 8–9, received an additional rhGH dose on Day 8 and had four dialysis sessions over the 9-day period.
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fig01: Trial design. All subjects had eight visits to the trial centre, seven daily doses of rhGH and a follow-up visit (Days 16–19). Patients had an additional assessment visit on Days 8–9, received an additional rhGH dose on Day 8 and had four dialysis sessions over the 9-day period.

Mentions: This was an open, nonrandomized, parallel-group study, comprising eight visits for healthy subjects and nine visits for patients with ESRD. The following visits were included for all subjects (Fig. 1): screening visit, baseline visit (Days 0–1), outpatient visits (Days 2–6), assessment visit (Days 7–8) and a follow-up visit (Days 16–19). Patients with ESRD received haemodialysis treatment on alternate days three times during the study, and had an additional assessment visit (Days 8–9), which included a dialysis session. The first dose of rhGH (Norditropin® SimpleXx®, Novo Nordisk A/S, Bagsvaerd, Denmark) was administered in the evening of Day 1 and daily dosing continued up to Day 7. Patients received an additional dose on Day 8 in order to record the GH exposure during dialysis. All subjects received a dose of 50 µg/kg body weight (bw)/day (maximum 4 mg/day) by subcutaneous injection. In case of unacceptable side effects the dose was to be lowered by 25% to 38 µg/kg/day for the rest of the study.


Pharmacokinetics and pharmacodynamics of growth hormone in patients on chronic haemodialysis compared with matched healthy subjects: an open, nonrandomized, parallel-group trial.

Langbakke IH, Nielsen JN, Skettrup MP, Harper A, Klitgaard T, Weil A, Engelhardt E, Lange M - Clin. Endocrinol. (Oxf) (2007)

Trial design. All subjects had eight visits to the trial centre, seven daily doses of rhGH and a follow-up visit (Days 16–19). Patients had an additional assessment visit on Days 8–9, received an additional rhGH dose on Day 8 and had four dialysis sessions over the 9-day period.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2366021&req=5

fig01: Trial design. All subjects had eight visits to the trial centre, seven daily doses of rhGH and a follow-up visit (Days 16–19). Patients had an additional assessment visit on Days 8–9, received an additional rhGH dose on Day 8 and had four dialysis sessions over the 9-day period.
Mentions: This was an open, nonrandomized, parallel-group study, comprising eight visits for healthy subjects and nine visits for patients with ESRD. The following visits were included for all subjects (Fig. 1): screening visit, baseline visit (Days 0–1), outpatient visits (Days 2–6), assessment visit (Days 7–8) and a follow-up visit (Days 16–19). Patients with ESRD received haemodialysis treatment on alternate days three times during the study, and had an additional assessment visit (Days 8–9), which included a dialysis session. The first dose of rhGH (Norditropin® SimpleXx®, Novo Nordisk A/S, Bagsvaerd, Denmark) was administered in the evening of Day 1 and daily dosing continued up to Day 7. Patients received an additional dose on Day 8 in order to record the GH exposure during dialysis. All subjects received a dose of 50 µg/kg body weight (bw)/day (maximum 4 mg/day) by subcutaneous injection. In case of unacceptable side effects the dose was to be lowered by 25% to 38 µg/kg/day for the rest of the study.

Bottom Line: However, the efficacy and safety of GH could be compromised by the potential for accumulation in the circulation.No major safety issues were identified.Results demonstrate a difference between patients and healthy subjects regarding GH AUC(0-24 h).

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacology, Novo Nordisk A/S, Bagsvaerd, Denmark.

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.

Design: This was an open, nonrandomized, single-centre parallel-group study lasting 8-9 days.

Subjects: 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.

Measurements: 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.

Show MeSH
Related in: MedlinePlus