The acute management of intrathecal methotrexate overdose: Pharmacologic rationale and guidelines

Abstract

INTRATHECAL METHOTREXATE TtlERAPY is now used widely for the prevention and treatment of meningeal leukemia and lymphoma. During the past year we have been consulted on more cases Of intrathecal methotrexate overdosage then in any previous year. In the study reported here we used a modified one-compartment pharmacologic model to suggest guidelines for the acute management of intrathecal methotrexate poisoning, and illustrate how the approach was applied to two patients. METHODS AND PHARMACOLOGIC RATIONALE A modified Single compartment model was used to predict the efficacy of cerebrospinal fluid withdrawal for removal of intrathecally administered drug. The compartment was takefi to represent the volume of drug distribution within the CSF (Vi,Cs~). As such, VJ s~ was not held constant but expressed as a function of time (t) after administration. This modification incorporates the ascent of drug in the subarachnoid space after intralumbar administration. The initial VD csF was taken as the volume of drug injected (Vo). The rate of V~ csF expansion during the initial phase or distribution was assumed tO be governed by CSF bulk flow. The latter was approximated by the rate of CSF production which in the model was assumed to be 30 ml/hour? Hence,