AJP - Regulatory, Integrative and Comparative Physiology, Vol 248, Issue 2 147-R156, Copyright © 1985 by American Physiological Society
Kinetic model for disposition of 6-mercaptopurine in monkey plasma and cerebrospinal fluid
D. G. Covell, P. K. Narang and D. G. Poplack
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.
