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  • 1
    Electronic Resource
    Electronic Resource
    Interactions of vinblastine and vincristine with methotrexate transport in isolated rat hepatocytes (1993)
    Springer
    Cancer chemotherapy and pharmacology 32 (1993), S. 209-214 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The accumulation of methotrexate (MTX) in the presence of vinblastine (VBL) and vincristine (VCR) was studied in isolated rat hepatocytes. In accordance with our recent study on vindesine (VDS), we found VBL and VCR to reduce net MTX accumulation significantly at 15 min after MTX addition. Drug concentrations of 100 μM VBL and 500 μM VCR led to 67% and 82% reductions in intracellular MTX, respectively. Since there was only a slight inhibition of MTX efflux by 100 μM VBL, the accumulation data demonstrate that the major effect of VBL is on MTX influx. Dixon-plot analyses are suggestive of competitive inhibition of the MTX influx, yielding inhibition constants (K i values) of 55 μM for VBL and 110 μM for VCR. Since theK i values correspond grossly to plasma levels obtained in humans shortly after the infusion of therapeutic doses of the vinca alkaloids studied herein, the interaction with MTX uptake could serve to diminish the toxicity of MTX to nonmalignant cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685837
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Renal and hepatic toxicity after high-dose 7-hydroxymethotrexate in the rat (1994)
    Springer
    Cancer chemotherapy and pharmacology 34 (1994), S. 119-124 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To examine directly the hepatic and renal toxicity of 7-hydroxymethotrexate (7-OH-MTX) without interference of the parent compound methotrexate (MTX), we purified and gave 100 mg/kg 7-OH-MTX to rats, a dose resulting in serum levels of 7-OH-MTX comparable with those achieved in the clinic after the administration of high-dose MTX (HD-MTX). After only 5 h, the 7-OH-MTX-treated rats demonstrated 2.6-fold increases in serum creatinine values and 2-fold elevations in serum aspartate aminotransferase (ASAT) levels as compared with the controls. Morphologic evidence of toxicity, however, was apparent only in the kidneys. Intraluminal cellular debris containing membranous material and deteriorated organelles was seen, but no precipitate of the delivered drug. The peak serum concentration of 7-OH was up to 939 μM, and concentrations of 7-OH-MTX declined triphasically, showing at1/2α value of 2.45 min, at1/2β value of 30.5 min, and a terminal half-life (t1/2γ) of 240 min. The total clearance value was 14.5 ml min−1 kg, and the postdistributional volume of distribution (Vβ) was 5070 ml/kg. Our results may indicate a direct toxic effect of 7-OH-MTX on kidney and liver cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685928
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Renal and hepatic toxicity after high-dose 7-hydroxymethotrexate in the rat (1994)
    Springer
    Cancer chemotherapy and pharmacology 34 (1994), S. 119-124 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. To examine directly the hepatic and renal toxicity of 7-hydroxymethotrexate (7-OH-MTX) without interference of the parent compound methotrexate (MTX), we purified and gave 100 mg/kg 7-OH-MTX to rats, a dose resulting in serum levels of 7-OH-MTX comparable with those achieved in the clinic after the administration of high-dose MTX (HD-MTX). After only 5 h, the 7-OH-MTX-treated rats demonstrated 2.6-fold increases in serum creatinine values and 2-fold elevations in serum aspartate aminotransferase (ASAT) levels as compared with the controls. Morphologic evidence of toxicity, however, was apparent only in the kidneys. Intraluminal cellular debris containing membranous material and deteriorated organelles was seen, but no precipitate of the delivered drug. The peak serum concentration of 7-OH was up to 939 μM, and concentrations of 7-OH-MTX declined triphasically, showing a t 1/2α value of 2.45 min, a t 1/2β value of 30.5 min, and a terminal half-life (t 1/2γ) of 240 min. The total clearance value was 14.5 ml min–1 kg, and the postdistributional volume of distribution (Vβ) was 5070 ml/kg. Our results may indicate a direct toxic effect of 7-OH-MTX on kidney and liver cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685928
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
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