6-Mercaptopurine: Total Body Autoradiograms and Plasma Concentration-Time Curves of 6MP and Metabolites from Marmoset Monkeys

Abstract

To study the body distribution of 6-mercaptopurine (6MP), [8-¹⁴ C]6MP was given by infusion to 2 marmoset monkeys at a dose rate of 5 mg/kg body weight/h for 1 and 4 h, respectively. Both experimental animals were sacrificed 2 h after the end of the drug infusion and instantly frozen at −70°C. Whole-body sagittal sections were made later. Blood samples were obtained regularly during the experiments to quantitate 6MP, 6MP riboside (6MPR), 6-thioxanthine, and 6-thiouric acid in plasma. The autoradiograms revealed extensive distribution of the ¹⁴C label. High levels of radioactivity were seen in liver, bile, and intestinal contents. Labeling of the central nervous system and bone marrow was obvious. The plasma concentration-time curves of 6MP and 6MPR attained steady-state concentrations of 30–40 μM and 6–12 μM, respectively. After stopping the infusion of the drug, the concentrations of 6MP and 6MPR became equal. 6MPR contributes to the biological effect of 6MP, as degradation of 6MPR results in 6MP. In studies on the pharmacokinetics and dynamics one should try to include all relevant metabolites of 6MP, both in plasma and in the cells.

Key Words:

• 6-mercaptopurine
• 6-mercaptopurine riboside
• thiopurines