Inhibition of hepatic metabolism of azathioprine in vivo

Gastroenterology. 1978 Jan;74(1):90-2.


Glutathione-mediated thiolysis of azathioprine in the liver is believed to be the main mechanism for the conversion of this drug to 6-mercaptopurine. This metabolic step was inhibited in vivo by pretreating rats with probenecid as indicated both by less hepatic glutathione depletion and by a greater proportion of unmetabolized azathioprine in the liver. Less hepatic gluthathione depletion was also found in the hyperbilirubinemic Gunn rat. These findings indicate that the conversion of azathioprine to 6-mercaptopurine in vovo is mediated enzymatically by the glutathione S-transferases.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Azathioprine / metabolism*
  • Glutathione / metabolism
  • Liver / metabolism*
  • Male
  • Mercaptopurine / metabolism
  • Probenecid / pharmacology*
  • Rats


  • Mercaptopurine
  • Glutathione
  • Azathioprine
  • Probenecid