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
SN - 0009-9236
VL - 71
SP - 162
EP - 168
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
IS - 3
ER -
