Prolongation of drug exposure in cerebrospinal fluid by encapsulation into DepoFoam

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 (...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1993-04, Vol.53 (7), p.1596-1598
Main Authors: SINIL KIM, SHIRIN KHABITI, HOWELL, S. B, MCCULLY, C, BALIS, F. M, POPLACK, D. G
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Biological and medical sciences
Chemotherapy
Cytarabine - administration & dosage
Cytarabine - cerebrospinal fluid
Drug Carriers
Drug Compounding
Half-Life
Injections, Spinal
Lipid Bilayers
Macaca mulatta
Male
Medical sciences
Pharmacology. Drug treatments
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Summary: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.
ISSN:0008-5472
1538-7445