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  • 1
    Electronic Resource
    Electronic Resource
    Pharmacology of intrathecal VP-16-213 in dogs (1992)
    Springer
    Journal of neuro-oncology 13 (1992), S. 211-215 
    Details
    ISSN: 1573-7373
    Keywords: intrathecal ; VP16
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary VP-16-213 is an anticancer drug that is active against a number of malignancies including small cell lung cancer, lymphoma, and leukemia which are often complicated by the development of leptomeningeal carcinomatosis. To investigate the potential usefulness of VP-16-213 for intrathecal administration, the pharmacology and toxicity of intrathecal VP-16-213 was determined. VP-16-213 at varying doses (0.01–1.0 mg · kg) was instilled intrathecally in dogs. Plasma, CSF, spinal cord, and brain tissue drug concentrations were determined by radiochemical and high performance liquid chromatography technique. Drug concentrations were strikingly higher in spinal cord tissue near the injection site compared to more distal cord sites. CSF concentration of VP-16-213 is 3–4 logs higher compared to concurrent plasma levels. Severe neurotoxicity occurred at the higher doses used. Due to limited diffusion and extremely low doses which could be used without life-threatening neurotoxicity, VP-16-213 does not appear to be a useful agent for intrathecal administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00172472
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Central nervous system pharmacology of Baker's antifolate (NSC139105) in man (1984)
    Springer
    Journal of neuro-oncology 2 (1984), S. 187-193 
    Details
    ISSN: 1573-7373
    Keywords: Baker's antifolate ; metabolites ; CNS pharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Radiolabelled Baker's Antifolate (BAF) was administered to 6 patients undergoing surgical resection of intracerebral tumors. Levels of radioactivity in resected tumor and edematous brain adjacent to tumor were generally higher than levels in concurrent plasma samples and were generally comparable to levels in temporalis muscle. Levels in tumor cyst fluid were far lower than concurrent plasma levels and levels in surrounding tumor. Chromatography was performed on tumor from 2 patients and revealed that only a small proportion of the radioactivity represented unchanged BAF. The major metabolite present in tissues was 1 000 times less potent as an inhibitor of dihydrofolate reductase than was BAF. Five patients had cerebrospinal fluid (CSF) sampled following administration of tracer doses of radio-labelled BAF. Radioactivity levels were far lower in CSF than in plasma. Levels of radioactivity in the CSF were also far lower than levels in tumor and brain samples from other patients and were slightly lower than tumor cyst fluid levels. Two patients had CSF collected after they received therapeutic doses of BAF. In these patients, both CSF and plasma were assayed using a dihydrofolate reductase inhibition assay. As with tracer dose studies, CSF concentrations of BAF were substantially lower than were concurrent plasma concentrations. Thus it appears that only very low concentrations of BAF are attainable in human CSF and intracerebral tumor, although a metabolite which is a very weak inhibitor of dihydrofolate reductase attains high concentrations in tumor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00253270
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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