TY - JOUR

T1 - Effect of growth hormone on hepatic cytochrome P450 activity in healthy elderly men

AU - Jürgens, Gesche

AU - Lange, Kai Henrik Wiborg

AU - Reuther, Lene Ørskov

AU - Rasmussen, Birgitte Buur

AU - Brøsen, Kim

AU - Christensen, Hanne Rolighed

PY - 2002/3

Y1 - 2002/3

N2 - OBJECTIVE: Our objective was to study the effect of recombinant human growth hormone (rhGH) on hepatic cytochrome P450 (CYP) activity in 30 healthy elderly men.METHODS: The study was carried out as a randomized, double-blind, placebo-controlled parallel-group study. rhGH or placebo was administered for a period of 12 weeks. CYP activity was measured before, after 12 weeks of rhGH and placebo administration, and at 4 weeks after termination of rhGH and placebo administration with use of the biomarker reactions of CYP1A2 (caffeine), CYP2C19 (mephenytoin), CYP2D6 (sparteine), CYP3A4 (endogenous cortisol metabolism), and antipyrine clearance as common markers of CYP activity.RESULTS: The metabolic ratio of caffeine increased significantly in the group that received growth hormone compared with placebo (median difference, 4.55; 95% confidence interval (CI), 1.64 to 8.60; versus -0.90; 95% CI, -5.70 to 1.36), indicating an induction of CYP1A2. Moreover, the S/R ratio of mephenytoin showed a small but significant increase (median difference, 0.02; 95% CI, 0 to 0.31; versus 0; 95% CI, -0.01 to 0.06), indicating an inhibition of CYP2C19. There were no significant changes of the metabolic ratios of cortisol and sparteine or the antipyrine clearance compared with placebo.CONCLUSIONS: These results indicate that growth hormone induces CYP1A2 and, to a lesser extent, inhibits CYP2C19 in elderly men, but it exerts no effects on CYP2D6 and CYP3A4. Although the induction of CYP1A2 may be of some clinical relevance, the small inhibition of CYP2C19 is probably unimportant.

AB - OBJECTIVE: Our objective was to study the effect of recombinant human growth hormone (rhGH) on hepatic cytochrome P450 (CYP) activity in 30 healthy elderly men.METHODS: The study was carried out as a randomized, double-blind, placebo-controlled parallel-group study. rhGH or placebo was administered for a period of 12 weeks. CYP activity was measured before, after 12 weeks of rhGH and placebo administration, and at 4 weeks after termination of rhGH and placebo administration with use of the biomarker reactions of CYP1A2 (caffeine), CYP2C19 (mephenytoin), CYP2D6 (sparteine), CYP3A4 (endogenous cortisol metabolism), and antipyrine clearance as common markers of CYP activity.RESULTS: The metabolic ratio of caffeine increased significantly in the group that received growth hormone compared with placebo (median difference, 4.55; 95% confidence interval (CI), 1.64 to 8.60; versus -0.90; 95% CI, -5.70 to 1.36), indicating an induction of CYP1A2. Moreover, the S/R ratio of mephenytoin showed a small but significant increase (median difference, 0.02; 95% CI, 0 to 0.31; versus 0; 95% CI, -0.01 to 0.06), indicating an inhibition of CYP2C19. There were no significant changes of the metabolic ratios of cortisol and sparteine or the antipyrine clearance compared with placebo.CONCLUSIONS: These results indicate that growth hormone induces CYP1A2 and, to a lesser extent, inhibits CYP2C19 in elderly men, but it exerts no effects on CYP2D6 and CYP3A4. Although the induction of CYP1A2 may be of some clinical relevance, the small inhibition of CYP2C19 is probably unimportant.

KW - Aged

KW - Aged, 80 and over

KW - Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics

KW - Antipyrine/pharmacokinetics

KW - Cytochrome P-450 Enzyme System/metabolism

KW - Double-Blind Method

KW - Growth Hormone/adverse effects

KW - Humans

KW - Hydrocortisone/urine

KW - Insulin-Like Growth Factor I/metabolism

KW - Liver/drug effects

KW - Male

U2 - 10.1067/mcp.2002.121373

DO - 10.1067/mcp.2002.121373

M3 - Journal article

C2 - 11907490

VL - 71

SP - 162

EP - 168

JO - Clinical Pharmacology and Therapeutics

JF - Clinical Pharmacology and Therapeutics

SN - 0009-9236

IS - 3

ER -