Kinetics of mercaptopurine and thioguanine nucleotides in renal transplant recipients during azathioprine treatment

Ther Drug Monit. 1994 Feb;16(1):13-20. doi: 10.1097/00007691-199402000-00002.


The purpose of this study was to examine the pharmacokinetics of mercaptopurine (6-MP) and thioguanine nucleotides (6-TGN) during azathioprine treatment. Plasma profiles and urinary excretion of 6-MP and 6-TGN concentrations in red blood cells (RBCs) were measured repeatedly during the first 3 weeks following transplantation in 10 adults, who had received kidney grafts from living related donors. Mean maximal 6-MP plasma concentration (Cmax) was 340 nmol/L (SD = 290), mean time to Cmax (Tmax) was 2 h (SD = 1.8), and mean area under the plasma concentration-time curve (AUC) was 930 nmol/L/h (SD = 770). The mean fraction of azathioprine dose excreted as 6-MP in urine was 1.32% (SD = 1.11). Up to eightfold variability of Cmax and AUC was observed from day to day within each patient. The correlation between 6-MP AUC and amount excreted in the urine was weak (r = 0.37, 95% CI from 0.02 to 0.64). In this group of patients the observed 6-TGN levels in RBCs were low; maxima during the observation period ranged from undetectable to 250 pmol/8 x 10(8) RBCs. In individual patients, 6-TGN levels were relatively stable throughout the dosing interval ("within-dose-interval-CV" < 19%), even when sharp and high 6-MP peaks in plasma were observed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Azathioprine / pharmacokinetics*
  • Azathioprine / therapeutic use
  • Biotransformation
  • Drug Interactions
  • Erythrocytes / metabolism
  • Female
  • Humans
  • Kidney Transplantation / physiology*
  • Male
  • Mercaptopurine / blood
  • Mercaptopurine / pharmacokinetics*
  • Mercaptopurine / urine
  • Middle Aged
  • Thioguanine / blood
  • Thioguanine / pharmacokinetics*
  • Thioguanine / urine


  • Mercaptopurine
  • Thioguanine
  • Azathioprine