Kinetics of mercaptopurine and thioguanine nucleotides in renal transplant recipients during azathioprine treatment.
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.
Bergan
S
S
Institute of Clinical Biochemistry, National Hospital, University of Oslo, Norway.
Rugstad
H E
HE
Bentdal
O
O
Endresen
L
L
Stokke
O
O
D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001711:Biotransformation; D004347:Drug Interactions; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D015122:Mercaptopurine / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008875:Middle Aged; D013866:Thioguanine / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
D015122:Mercaptopurine; D013866:Thioguanine; D001379:Azathioprine