Interaction of azathioprine and glutathione in the liver of the rat.
Azathioprine was administered to rats in order to study its interaction with glutathione in vivo. Glutathione levels were measured sequentially in liver, red blood cells, kidney and small intestine after i.p. injections of azathioprine (6.25-100 micronmol/100 g b.wt.). Five minutes after drug administration, dose-related selective depletion of hepatic glutathione up to 50% of control was observed. By 60 minutes 80% depletion of hepatic glutathione was observed. Red cell glutathione depletion was also observed but lagged behind hepatic changes. Five minutes after azathioprine administrations, no change in red cell glutathione was seen with all doses of azathioprine, but a dose-related increase in plasma 6-mercaptopurine and azathioprine was observed. At all azathioprine doses and at all time intervals after drug administration, the hepatic contribution to total glutathione consumption predominated. No change in glutathione levels in kidney or small intestine was observed after azathioprine. Thus, the liver plays a major role in the metabolism of azathioprine through the interaction of the drug with glutathione.
D000818:Animals; D001379:Azathioprine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004912:Erythrocytes / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D051381:Rats
D005978:Glutathione; D001379:Azathioprine