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  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of BW12C and mitomycin C, given in combination in a phase 1 study in patients with advanced gastrointestinal cancer (1993)
    Springer
    Cancer chemotherapy and pharmacology 32 (1993), S. 67-72 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of combining the oxygen-transport-modifying drug BW12C with mitomycin C was investigated in a phase 1 study of 26 patients with advanced gastrointestinal cancer. The dose of BW12C was increased from 20 mg/kg to 60 mg/kg. Dose-limiting toxicity of vomiting was experienced at doses greater than 50 mg/kg. This corresponded to whole blood levels ≥700 μg/ml and to 〉50% haemoglobin modification. Whole blood concentrations of BW12C and modification of the haemoglobin oxygen saturation curve were linearly dependent on dose. BW12C whole blood pharmacokinetics were best described by a one-compartment model and were clearly dose-dependent. The half-life increased from 2.1 h at a dose of 20 mg/kg to 7.2 h at a dose of 60 mg/kg. The AUC increased in a similar non-linear fashion with increasing dose. Mitomycin C was given at a fixed dose of 20 mg/m2 at the end of the BW12C infusion. Mitomycin C plasma pharmacokinetics fitted a two-compartment model, giving a mean beta half-life of 50±7 min and AUC of 1.1±0.08 μg/ml h, and were unaffected by the combined treatment. There was no evidence of increased mitomycin C toxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685879
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    Paper (German National Licenses)
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  • 2
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    The Road to Curing Cancer (1980)
    London : Periodicals Archive Online (PAO)
    RSA Journal. 128:5282 (1980:Jan.) 92 
    Details
    ISSN: 0958-0433
    Topics: Art History
    Description / Table of Contents: Two Cantor Lectures on ASPECTS OF MODERN MEDICINE
    Notes: PROCEEDINGS OF THE SOCIETY
    URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pao:&rft_dat=xri:pao:article:q549-1980-128-82-000010
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Clinical pharmacokinetics of oral CCNU (Lomustine) (1985)
    Springer
    Cancer chemotherapy and pharmacology 14 (1985), S. 125-131 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The plasma pharmacokinetics of orally administered CCNU (130 mg/m2) were studied in four patients using reversed-phase high-performance liquid chromatography (HPLC) analysis. Parent CCNU was not detected in the plasma of any of the patients, probably due to complete conversion to monohydroxylated metabolites during the ‘first pass’ through liver and gut. However, two monohydroxylated metabolites, trans-4-hydroxy CCNU and cis-4-hydroxy CCNU, were found at high concentrations, the relative amounts being about 6 : 4. Peak concentrations of the metabolites were reached 2–4 h after administration and were remarkably similar for all four patients, the total being 0.8–0.9 μg/ml. The metabolites were also detected in a tumour biopsy. Plasma clearance half-lives of the two metabolites were similar in each patient but showed a two-fold variation between patients, from 1.3 to 2.9 h. These results suggest that the antitumour activity and systemic toxicity of CCNU when given orally are due mainly to its monohydroxylated metabolites. Finally, comparison with data obtained in vitro and in mice showed that the nitrosourea exposures in these patients were at the lower limit of those required for significant antineoplastic activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00434350
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Lack of stereoselectivity in the pharmacokinetics and metabolism of the radiosensitizer Ro 03-8799 in man (1991)
    Springer
    Cancer chemotherapy and pharmacology 28 (1991), S. 118-122 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary During a clinical toxicity study it was possible to obtain urine samples from six patients receiving either the R-(−)- or S-(+)-stereoenantiomeric forms of the developmental 2-nitroimidazole radiosensitizer Ro 03-8799 (pimonidazole). Paired plasma samples were also obtained from four patients. The pharmacokinetic data were compared with those for the racemic mixture in the same individuals. The results revealed no major differences in the plasma pharmacokinetics, urinary clearance orN-oxidation of the individual enantiomers as compared with the racemic mixture. A similar lack of steroselectivity with respect to the acute dose-limiting CNS toxicity syndrome suggests that this may not involve a specific CNS receptor interaction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689700
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    Paper (German National Licenses)
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