Journal
JOURNAL OF NEURO-ONCOLOGY
Volume 81, Issue 2, Pages 201-208Publisher
SPRINGER
DOI: 10.1007/s11060-006-9218-x
Keywords
encapsulated cytarabine; DepoCyt (R); Ara-C; cytosine arabinoside; neoplastic meningitis; pharmacokinetics
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Introduction Cytarabine liposome injection (DepoCyt(R)), a sterile suspension of the antimetabolite cytarabine, encapsulated into multivesicular, lipid-based particles, has been developed to improve the treatment of neoplastic meningitis (NM) through sustained release of cytarabine. The objective of this study was to determine the pharmacokinetics (PK) of cytarabine after intrathecal administration of 50 mg encapsulated cytarabine (DepoCyt(R)) in patients with neoplastic meningitis up to 336 h (14 days) after dosing. Methods This was an open-label study wherein two 50-mg doses of DepoCyt(R) were administered 14 days apart via the intraventricular (IVT) route or by lumbar puncture (LP). Cerebrospinal fluid (CSF) samples were collected from eight adult patients at various times up to 14 days after each dose. Plasma samples were also collected within the same time period. CSF samples were analyzed for unencapsulated (free) and encapsulated cytarabine and the cytarabine metabolite, ara-U. Plasma samples were analyzed for free cytarabine and ara-U. The limit of detection was 0.003 mu g/mL cytarabine and 0.016 mu g/ml for ara-U. Results The concentration of free and encapsulated cytarabine in the ventricular and lumbar CSF ranged from 0.01 to 1500 mu g/mL and were detectable up to 14 days post-dosing. Free cytarabine concentrations in plasma were only sporadically detectable. CSF and plasma concentrations of ara-U were low in all samples. Conclusions The administration of intrathecal encapsulation cytarabine prolongs sustained tumor exposure to cytotoxic concentrations of cytarabine (> 0.02 mu g/ml) with a slow continuous release of cytarabine from the DepoFoam(TM) particles, so drug exposure is prolonged over time, resulting in lower peak cytarabine levels and a longer duration of exposure compared with standard cytarabine (Ara-C).
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