title: Effects of chronic hypoxia on the pharmacokinetics of caffeine and cardio-green in micro swine.
abstract: METHODS
  The pharmacokinetics of caffeine and cardio-green (ICG) were examined in four micro swine at sea level (SEA) and following 21 d continuous exposure to 4600 m (ALT) in a hypobaric chamber. Caffeine (84.7 mg) and ICG (10 mg) were administered as separate intravenous boluses and sequential blood samples collected.
  
  
  RESULTS
  Caffeine clearance significantly (p < 0.05) increased in ALT (96.8 +/- 20.0 ml.min-1) as compared to SEA (53.6 +/- 24.8 ml.min-1), demonstrating that liver function increased in ALT. There was no significant change in the ratio of primary metabolites to caffeine, suggesting that the increase in clearance was not due to a change in the rate of caffeine metabolism. ICG clearance significantly increased in ALT (179.8 +/- 57.4 ml.min-1) as compared to SEA (84.4 +/- 28.9 ml.min-1) indicating that hepatic blood flow (HBF) increased.
  
  
  CONCLUSIONS
  These results demonstrate that chronic exposure to 4600 m increases the clearance of caffeine and ICG in the micro swine model and suggests that the increase in caffeine clearance is related to HBF.
authors.affiliation: Department of Behavioral Biology, Walter Reed Army Medical Institute of Research, Washington, DC 20307-5100, USA.
authors.forename: G H
authors.initials: GH
authors.lastname: Kamimori
authors.forename: R W
authors.initials: RW
authors.lastname: Hoyt
authors.forename: N D
authors.initials: ND
authors.lastname: Eddington
authors.forename: P M
authors.initials: PM
authors.lastname: Young
authors.forename: M J
authors.initials: MJ
authors.lastname: Durkot
authors.forename: V A
authors.initials: VA
authors.lastname: Forte
authors.forename: A E
authors.initials: AE
authors.lastname: Brunhart
authors.forename: S
authors.initials: S
authors.lastname: Lugo
authors.forename: A
authors.initials: A
authors.lastname: Cymerman
mesh_terms: D000531:Altitude; D000818:Animals; D002110:Caffeine / Q000493:pharmacokinetics*; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D000860:Hypoxia / Q000378:metabolism*; D007208:Indocyanine Green / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D013552:Swine; D013556:Swine, Miniature
chemical_list: D002110:Caffeine; D007208:Indocyanine Green