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  • 1
    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
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    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    Evaluation of methotrexate tissue exposure by in situ microdialysis in a rat model (1994)
    Springer
    Cancer chemotherapy and pharmacology 34 (1994), S. 297-301 
    Details
    ISSN: 1432-0843
    Keywords: Microdialysis ; Methotrexate ; Tissue ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The feasibility of using a microdialysis technique to obtain pharmacokinetic data on tissue exposure to methotrexate (MTX) was investigated. Microdialysis probes were implanted in the jugular vein, femoral muscle, and liver ofanesthetized male Wistar rats. MTX (100 mg/kg) was given as a bolus injection through an indwelling venous catheter, and blood samples were obtained through a second venous access and by microdialysis for a total of 6 h. Heparinized plasma, ultrafiltered plasma, and microdialysis effluent from tissue and venous probes were analyzed by high-performance liquid chromatography. Centrifugal ultrafiltration of rat plasma spiked in vitro with MTX (1–100 μM) revealed a mean binding to plasma proteins of 21%. In vitro microdialysis of this spiked plasma resulted in 23% relative recovery of the unbound fraction. In rats receiving MTX, plasma protein binding was 23% and the relative drug recovery as assessed with venous microdialysis probes was 18%. Plotting of unbound (i.e., ultrafiltrate) MTX concentrations in the blood against venous microdialysis perfusate values in the blood gave a good linear correlation with a coefficient of correlation (r 2) of 0.98. There was also a linear correlation between the total MTX concentrations in venous blood and the drug levels in microdialysis samples from muscle and liver (r 2=0.93 and 0.74, respectively). Area under the curve estimations were consistent with an MTX exposure of 30% and 46% for the muscle and liver as compared with the circulation. The present study demonstrates that the microdialysis technique can provide reproducible data on tissue exposure to MTX in an animal model and indicates that the methodology is adaptable to clinical settings.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686036
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Quantition of cell-associated doxorubicin by high-performance liquid chromatography after enzymatic desequestration (1994)
    Springer
    Cancer chemotherapy and pharmacology 34 (1994), S. 197-202 
    Details
    ISSN: 1432-0843
    Keywords: Doxorubicin ; HPLC ; Cellular concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A method for measuring cellular concentrations of the anthracycline doxorubicin was developed. The assay involves cell lysis and protein degradation by detergent and proteinase K treatment followed by DNA hydrolysis using DNase I. Prior to high-performance liquid chromatography, samples are deproteinized by the addition of ZnSO4 and methanol. The assay is linear with respect to both the cellular drug content and the number of cells assayed over the ranges tested, and drug recovery is close to 100%. The method has a limit of detection of 50 fmol injected doxorubicin. Within run and between-day coefficients of variation have consistently been found to be in the 5% and 10% range, respectively, in different cell lines exposed to doxorubicin in vitro. The method has been evaluated in analyses of doxorubicin levels in mononuclear blood cells of patients. The assay offers several advantages over commonly used organic extraction techniques and may improve cellular drug monitoring during anthracycline therapy in patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685077
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Quantitation of cell-associated doxorubicin by high-performance liquid chromatography after enzymatic desequestration (1994)
    Springer
    Cancer chemotherapy and pharmacology 34 (1994), S. 197-202 
    Details
    ISSN: 1432-0843
    Keywords: Key words: Doxorubicin – HPLC – Cellular concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. A method for measuring cellular concentrations of the anthracycline doxorubicin was developed. The assay involves cell lysis and protein degradation by detergent and proteinase K treatment followed by DNA hydrolysis using DNase I. Prior to high-performance liquid chromatography, samples are deproteinized by the addition of ZnSO4 and methanol. The assay is linear with respect to both the cellular drug content and the number of cells assayed over the ranges tested, and drug recovery is close to 100%. The method has a limit of detection of 50 fmol injected doxorubicin. Within run and between-day coefficients of variation have consistently been found to be in the 5% and 10% range, respectively, in different cell lines exposed to doxorubicin in vitro. The method has been evaluated in analyses of doxorubicin levels in mononuclear blood cells of patients. The assay offers several advantages over commonly used organic extraction techniques and may improve cellular drug monitoring during anthracycline therapy in patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685077
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 5
    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
  • 6
    Electronic Resource
    Electronic Resource
    Evaluation of methotrexate tissue exposure by in situ microdialysis in a rat model (1994)
    Springer
    Cancer chemotherapy and pharmacology 34 (1994), S. 297-301 
    Details
    ISSN: 1432-0843
    Keywords: Key words: Microdialysis – Methotrexate – Tissue – Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The feasibility of using a microdialysis technique to obtain pharmacokinetic data on tissue exposure to methotrexate (MTX) was investigated. Microdialysis probes were implanted in the jugular vein, femoral muscle, and liver of anesthetized male Wistar rats. MTX (100 mg/kg) was given as a bolus injection through an indwelling venous catheter, and blood samples were obtained through a second venous access and by microdialysis for a total of 6 h. Heparinized plasma, ultrafiltered plasma, and microdialysis effluent from tissue and venous probes were analyzed by high-performance liquid chromatography. Centrifugal ultrafiltration of rat plasma spiked in vitro with MTX (1 – 100 μM) revealed a mean binding to plasma proteins of 21%. In vitro microdialysis of this spiked plasma resulted in 23% relative recovery of the unbound fraction. In rats receiving MTX, plasma protein binding was 23% and the relative drug recovery as assessed with venous microdialysis probes was 18%. Plotting of unbound (i. e., ultrafiltrate) MTX concentrations in the blood against venous microdialysis perfusate values in the blood gave a good linear correlation with a coefficient of correlation (r 2) of 0.98. There was also a linear correlation between the total MTX concentrations in venous blood and the drug levels in microdialysis samples from muscle and liver (r 2 = 0.93 and 0.74, respectively). Area under the curve estimations were consistent with an MTX exposure of 30% and 46% for the muscle and liver as compared with the circulation. The present study demonstrates that the microdialysis technique can provide reproducible data on tissue exposure to MTX in an animal model and indicates that the methodology is adaptable to clinical settings.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686036
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 7
    Electronic Resource
    Electronic Resource
    Intrauterine fertilization capsules—A clinical trial (1991)
    Springer
    Journal of assisted reproduction and genetics 8 (1991), S. 272-275 
    Details
    ISSN: 1573-7330
    Keywords: intrauterine capsules ; capsule treatment ; in vivo fertilization ; insemination capsules ; encapsulated intrauterine insemination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Treatment of 26 women with tubal infertility was attempted using intrauterine capsules loaded with oocytes and spermatozoa. The stimulation protocol was as used for in vitro fertilization and embryo transfer and consisted of short-term use of Buserelin, human menopausal gonadotropin, and human chorionic gonadotropin. Oocytes were collected by ultrasonically guided transvaginal aspiration, and spermatozoa were prepared by swim-up technique. The gametes were placed in agar capsules 4 hr after oocyte collection, and the capsules were introduced to the uterine fundus using an insertion tube and piston from an intrauterine device. Six complete capsules and parts of two other capsules were expelled. None of the women became pregnant, compared with a pregnancy rate of 21% per aspiration following in vitro fertilization and embryo transfer during the same period.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01139783
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
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