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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

Individual (narrow lines) and mean (thick lines) GH profiles for patients (top) and healthy subjects (bottom) on Days 7–8. Inserts show individual profiles on Day 1.
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fig02: Individual (narrow lines) and mean (thick lines) GH profiles for patients (top) and healthy subjects (bottom) on Days 7–8. Inserts show individual profiles on Day 1.

Mentions: The GH AUC0–12 h geometric mean at steady-state for patients was almost double that for healthy subjects (Table 3). Based on the 90% CI, a difference between patients and healthy subjects was indicated for this and all other secondary PK end-points. The geometric mean GH AUC18–24 h at steady-state for healthy subjects was double that for patients. Individual/mean GH profiles on Days 7–8 are shown in Fig. 2. Of particular note is the fact that GH concentrations for both patients and healthy subjects were comparable with baseline values by about 20–22 h, demonstrating that administered rhGH does not seem to be retained in the circulation of patients with ESRD. Moreover, the geometric mean GH AUC18–24 h steady-state for both patients and healthy subjects (Table 3) was about the same as the baseline mean values (Table 2). Individual GH profiles (not shown) for the period 18–24 h on Days 7–8 were relatively flat compared to the peaks obtained on Day 1 for all subjects (particularly noticeable for the patient group) (Fig. 2, inserts), demonstrating that administration of rhGH appeared to suppress endogenous GH production.


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)

Individual (narrow lines) and mean (thick lines) GH profiles for patients (top) and healthy subjects (bottom) on Days 7–8. Inserts show individual profiles on Day 1.
© Copyright Policy
Related In: Results  -  Collection

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

fig02: Individual (narrow lines) and mean (thick lines) GH profiles for patients (top) and healthy subjects (bottom) on Days 7–8. Inserts show individual profiles on Day 1.
Mentions: The GH AUC0–12 h geometric mean at steady-state for patients was almost double that for healthy subjects (Table 3). Based on the 90% CI, a difference between patients and healthy subjects was indicated for this and all other secondary PK end-points. The geometric mean GH AUC18–24 h at steady-state for healthy subjects was double that for patients. Individual/mean GH profiles on Days 7–8 are shown in Fig. 2. Of particular note is the fact that GH concentrations for both patients and healthy subjects were comparable with baseline values by about 20–22 h, demonstrating that administered rhGH does not seem to be retained in the circulation of patients with ESRD. Moreover, the geometric mean GH AUC18–24 h steady-state for both patients and healthy subjects (Table 3) was about the same as the baseline mean values (Table 2). Individual GH profiles (not shown) for the period 18–24 h on Days 7–8 were relatively flat compared to the peaks obtained on Day 1 for all subjects (particularly noticeable for the patient group) (Fig. 2, inserts), demonstrating that administration of rhGH appeared to suppress endogenous GH production.

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