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Related Experiment Videos

Growth hormone replacement therapy induces codeine clearance.

E Gil Berglund1, G Johannsson, O Beck

  • 1The Medical Products Agency, Uppsala, Sweden.

European Journal of Clinical Investigation
|August 3, 2002
PubMed
Summary
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Growth hormone (GH) replacement therapy significantly increases codeine clearance, primarily by enhancing UDP-glucuronosyl transferase (UDPGT) activity. This impacts drug metabolism and may affect steroid hormone levels.

Area of Science:

  • Pharmacology
  • Endocrinology
  • Hepatology

Background:

  • Clinical use of growth hormone (GH) necessitates understanding its non-growth-related metabolic effects.
  • GH influences hepatic drug-metabolizing enzymes in rats, but human effects remain unclear.
  • Investigated GH impact on key drug-metabolizing enzymes: cytochrome P450 (CYP3A, CYP2D6) and UDP-glucuronosyl transferase (UDPGT).

Purpose of the Study:

  • To determine the effect of GH substitution therapy on the metabolic clearance of codeine in GH-deficient patients.
  • To assess GH's influence on the activity of hepatic enzymes UDP-glucuronosyl transferase (UDPGT) and cytochrome P450 (CYP3A, CYP2D6).

Main Methods:

  • Codeine was administered as a probe drug before and after 3 months of GH substitution in GH-deficient patients.

Related Experiment Videos

  • Total codeine clearance and clearance via its primary metabolic pathways were assessed.
  • Enzyme activities were evaluated by measuring codeine metabolism through UDPGT and CYP pathways.

    • Main Results:

    • Three months of GH substitution significantly increased total codeine clearance by 21% (P < 0.01).
    • UDPGT-catalyzed codeine clearance increased significantly by 31% (P < 0.05).
    • A trend towards increased clearance via the CYP3A pathway was observed (83%, P = 0.05).

    Conclusions:

    • GH replacement therapy alters drug metabolism, particularly affecting UDPGT and CYP3A pathways.
    • Clinical implications exist for patients on GH therapy receiving drugs metabolized by UDPGT and CYP3A.
    • Potential endocrine consequences due to altered steroid hormone metabolism cannot be excluded.