Kinetic model for disposition of 6-mercaptopurine in monkey plasma and cerebrospinal fluid

The antipurine 6-mercaptopurine (6-MP) is effective in the induction and maintenance of remission in patients with acute lymphocytic leukemia. This report presents a compartmental model that describes the kinetics of 6-MP in the plasma and cerebrospinal fluid (CSF) of the monkey. Analysis is based on simultaneously measured plasma and CSF 6-MP concentrations after intravenous and intraventricular bolus administration. Results indicate that 6-MP administered intraventricularly remains largely in the CSF. Disappearance of 6-MP from CSF is principally due to convective losses at a rate equivalent to CSF turnover. Diffusion of 6-MP across the ependymal surface accounts for only 7% of the 6-MP appearing in the plasma. Conversely the dominant route for entry of 6-MP into the CSF from the plasma is entrainment in choroidally formed CSF. Only 12% of 6-MP in the CSF after intravenous administration can be accounted for by permeation of cerebral capillaries and diffusion through brain parenchyma and across the ependymal surface into CSF. These results indicate that the choroid plexus is not a significant barrier for the transfer of molecules like 6-MP from plasma to CSF.