EXTENDED CSF CYTARABINE EXPOSURE FOLLOWING INTRATHECAL ADMINISTRATION OF DTC-101

Purpose: The aims of the present study were to determine ventricular and lumbar CSF pharmacokinetics and the maximum-tolerated dose (MTD) of DTC 101 (DepoFoam; DepoTech Corp, La Jolla, CA) following intraventricular administration. Patients and Methods: Twelve patients with neoplastic meningitis were treated with escalating doses of DTC 101. CSF samples were obtained from the right lateral ventricle or from the lumbar subarachnoid space and cytarabine concentrations were determined by high-performance liquid chromatography. Results: Therapeutic ventricular CSF concentrations were maintained for 9 ± 2 days following administration of a single dose of DTC 101 into the lateral ventricle. Lumbar cytarabine concentrations became equal to those in the ventricle within the first 6 hours after intraven-tricular injection, and the subsequent decay in concentrations of free and total cytarabine were the same at both sites. Following intralumbar administration, the peak ventricular concentration of free cytarabine was reached within 1 day, and therapeutic ventricular CSF levels were maintained for several days. Therapeutic intralumbar concentration of free cytarabine was maintained for up to 14 days. The MTD was 75 mg of DTC 101, and seven of nine patients manifested cytologic responses. Conclusion: Extended CSF exposure to therapeutic cytarabine concentrations was achieved after a single intraventricular or intralumbar dose of DTC 101, permitting drug administration once every 2 weeks.