A new rhesus monkey model with two intraventricular
catheter systems was developed to examine the pharmacokinetics and neurotoxicity of chemotherapeutic agents administered by continuous
intraventricular infusion. A lateral ventricular
catheter system implanted in the lateral ventricle and attached to a subcutaneous access port on the animal's back is used for infusion of drugs into the ventricle. A Pudenz
catheter implanted in the fourth ventricle and connected to a subcutaneous Ommaya reservoir permits repetitive CSF sampling in unanesthetized animals. The model was evaluated in five animals for over 12 months for
catheter patency, surgical complications, and utility in studying the pharmacokinetics of continuous
intraventricular infusion of
methotrexate. There were no perioperative complications. Three of the five monkeys maintained both systems successfully. The other two animals developed staphylococcal ventriculitis, one at 7 days as a result of manipulation of the incision by the animal leading to
cellulitis around the
catheter site and subsequent ventriculitis, the other at 5 months. Both animals were treated successfully with
antibiotics and
catheter removal. An infusion of 0.05 mg of
methotrexate over 24 hours maintained ventricular
drug concentrations of 1 mol/L without evidence of neurotoxicity. This new model has applications both for the development of continuous
intraventricular infusion as a therapeutic approach for the treatment of
meningeal cancers in humans and as a research tool to study the distribution and elimination of drugs from the CSF.