title: Prolongation of drug exposure in cerebrospinal fluid by encapsulation into DepoFoam.
abstract: Prolonged maintenance of a therapeutic drug concentration in the cerebrospinal fluid is required for optimal treatment of leptomeningeal leukemia or carcinomatosis with cell cycle-specific antimetabolites. The pharmacokinetics of 1-beta-D-arabinofuranosylcytosine (ara-C) encapsulated into DepoFoam (Depo/Ara-C) was studied in six rhesus monkeys after intrathecal injection into the lumbar sac. Following a single 2-mg dose, the Depo/Ara-C concentration decreased biexponentially with initial and terminal half-lives of 14.6 and 156 h, respectively. The free drug concentration remained above the reported minimal cytotoxic level of 0.1 micrograms/ml (0.4 microM) for more than 672 h (28 days). In contrast, the half-life of ara-C following an intralumbar bolus dose of unencapsulated drug in a single animal was 0.74 h. A single intrathecal injection of Depo/Ara-C can maintain a therapeutic drug concentration in the cerebrospinal fluid for a very prolonged period.
authors.affiliation: Department of Medicine, UCSD Cancer Center, La Jolla 92093.
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Khatibi
authors.forename: S B
authors.initials: SB
authors.lastname: Howell
authors.forename: C
authors.initials: C
authors.lastname: McCully
authors.forename: F M
authors.initials: FM
authors.lastname: Balis
authors.forename: D G
authors.initials: DG
authors.lastname: Poplack
mesh_terms: D000818:Animals; D003561:Cytarabine / Q000008:administration & dosage / Q000134:cerebrospinal fluid*; D004337:Drug Carriers; D004339:Drug Compounding; D006207:Half-Life; D007278:Injections, Spinal; D008051:Lipid Bilayers; D008253:Macaca mulatta; D008297:Male
chemical_list: D004337:Drug Carriers; D008051:Lipid Bilayers; D003561:Cytarabine