Effect of growth hormone on hepatic cytochrome P450 activity in healthy elderly men.
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.
Jürgens
Gesche
G
Department of Clinical Pharmacology, Bispebjerg University Hospital, Copenhagen, Denmark.
Lange
Kai Henrik Wiborg
KH
Reuther
Lene Ørskov
LØ
Rasmussen
Birgitte Buur
BB
Brøsen
Kim
K
Christensen
Hanne Rolighed
HR
D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics; D000983:Antipyrine / Q000493:pharmacokinetics; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004311:Double-Blind Method; D013006:Growth Hormone / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D003577:Cytochrome P-450 Enzyme System; D000983:Antipyrine; D006854:Hydrocortisone