Effects of chronic hypoxia on the pharmacokinetics of caffeine and cardio-green in micro swine.
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.
Kamimori
G H
GH
Department of Behavioral Biology, Walter Reed Army Medical Institute of Research, Washington, DC 20307-5100, USA.
Hoyt
R W
RW
Eddington
N D
ND
Young
P M
PM
Durkot
M J
MJ
Forte
V A
VA
Brunhart
A E
AE
Lugo
S
S
Cymerman
A
A
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
D002110:Caffeine; D007208:Indocyanine Green