Intracerebral microdialysis for determination of the neuropharmacokinetics and neuropharmacodynamics of temozolomide in patients with primary or metastatic brain tumors

2074 Background: Microdialysis (MD) is a technique for continuously analyzing concentrations of endogenous chemicals and drugs in the extracellular fluid (ECF) of a body tissue. The purpose of this study is to apply MD to the determination of the neuropharmacokinetics (nPK) and neuropharmacodynamics (nPD) of temozolomide (TMZ) following systemic administration. Methods: After surgical debulking, a MD catheter is placed in peritumoral brain tissue. Artificial cerebrospinal fluid (CSF) is continuously perfused at a rate of 1 μl/min. Fused CT/MRI scans confirm correct placement of the catheter in non-enhancing brain. Starting 24 hrs after surgery, patients are given a dose of TMZ (150 mg/m2), and serial ECF and plasma samples are collected over 24 hrs. TMZ concentrations are determined by LC/MS/MS. In vitro recovery of TMZ via the MD catheter has been determined to be 87±5.5% at a flow rate of 1 μl/min. Prior to and 24 hrs post TMZ, additional ECF samples are collected for analysis of glucose, glutamate, lac...