EFFECT OF INTRAVENOUS DOSE AND SCHEDULE ON CEREBROSPINAL-FLUID PHARMACOKINETICS OF 5-FLUOROURACIL IN THE MONKEY

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (11) , 4929-4932
Abstract
There is little information regarding the pharmacology of 5-fluorouracil (5-FUra) in the CNS, despite its role in the treatment of diseases with CNS metastases and recent reports of neurotoxicity. In this study, the plasma and CSF pharmacokinetics of 5-UFra were examined in a primate model. Following a bolus dose, the area under the concentration vs. time curves for 5-FUra in CSF was 48% of the plasma area under the concentration vs. time curves. For continuous infusion of 5-FUra, the area under the concentration vs. time curves ratio for CSF:plasma was 20 or 11%, depending upon the infusion rate. The mechanism for variations in CSF exposure based upon the pattern of plasma delivery is consistent with local metabolism of 5-FUra in the CNS. These findings should be considered in the evaluation of delivery schedules which are intended to maximize drug delivery to the CNS and/or minimize neurotoxicity.