title: Acute hypoxia and cytochrome P450-mediated hepatic drug metabolism in humans.
abstract: OBJECTIVE
  Our objective was to investigate the effect of acute hypoxia on the activity of hepatic cytochrome P450 (CYP) enzymes.
  
  
  METHODS
  Twelve healthy subjects who lived at sea level were exposed to altitude-induced hypoxia for 7 days at 4559 m above sea level. Hepatic CYP enzyme activity was measured before departure, at 24 and 96 hours after arrival to high-altitude location, and at 1 month after return to sea level. CYP enzyme activities were measured by means of the metabolic ratios of sparteine (CYP2D6), endogenous cortisol metabolism (CYP3A4), and caffeine (CYP1A2), as well as by the S/R ratio of mephenytoin (CYP2C19) and antipyrine clearance.
  
  
  RESULTS
  The metabolic ratio of sparteine increased after 24 hours at high altitude (median difference, 0.15; 95% confidence interval, 0.05 to 0.28) and remained increased after 96 hours. The ratio decreased after return to sea level (median difference, -0.15; 95% confidence interval, -0.29 to -0.03; P =.016, Friedman test). The metabolic ratio of cortisol decreased after 24 hours (median difference, -2.0; 95% confidence interval, -3.5 to -0.5) but returned to sea level values after 96 hours at high altitude (median difference, 1.6; 95% confidence interval, 1.0 to 4.2; P =.047, Friedman test). These changes indicate a small decrease in the activity of CYP2D6 and CYP3A4. There were no significant changes regarding the metabolic ratio of caffeine, the S/R ratio of mephenytoin, or antipyrine clearance.
  
  
  CONCLUSIONS
  The small changes observed suggest that acute hypoxia has no clinically significant effects on CYP enzymes in humans.
authors.affiliation: Department of Clinical Pharmacology, Bispebjerg University Hospital, Copenhagen, Denmark. gesche@rh.dk
authors.forename: Gesche
authors.initials: G
authors.lastname: Jürgens
authors.forename: Hanne Rolighed
authors.initials: HR
authors.lastname: Christensen
authors.forename: Kim
authors.initials: K
authors.lastname: Brøsen
authors.forename: Jesper
authors.initials: J
authors.lastname: Sonne
authors.forename: Steffen
authors.initials: S
authors.lastname: Loft
authors.forename: Niels Vidiendal
authors.initials: NV
authors.lastname: Olsen
mesh_terms: D000208:Acute Disease; D000328:Adult; D000531:Altitude; D002110:Caffeine / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D000860:Hypoxia / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D008137:Longitudinal Studies; D008297:Male; D008617:Mephenytoin / Q000378:metabolism; D013034:Sparteine / Q000378:metabolism; D018709:Statistics, Nonparametric
chemical_list: D013034:Sparteine; D002110:Caffeine; D003577:Cytochrome P-450 Enzyme System; D008617:Mephenytoin; D006854:Hydrocortisone