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  • 1980-1984  (3)
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  • 1
    ISSN: 1432-1076
    Keywords: Gentamicin ; Nephrotoxicity ; Pharmaco-kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pharmacokinetics and nephrotoxicity of gentamicin were studied in female Wistar rats of different ages. I.m. administration of 5 mg of gentamicin/kg revealed that young rats (90 g) had lower peak serum levels and a prolonged elimination half-life, when compared with adult animals. After repeated injections, renal gentamicin concentrations were continuously lower in young rats during the entire experiment until the 20th day after the last dose. Nephrotoxicity, as measured by urinary excretion rates of tubular cells and malic dehydrogenase, was most pronounced in the old rats (260 g) and distinctly less in the 210 g animals. The young rats reacted with a slight but not significant increase in cellular and enzyme excretion. Since one cause of nephrotoxicity can be assumed to be intrarenal accumulation of gentamicin, it may be concluded that a deficient ability to concentrate aminoglycosides in the kidneys resulted in decreased nephrotoxic potential of gentamicin in the young rats.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die therapeutische Effektivität und Pharmakokinetik der Cephalosporine Ceftazidim, Ceftizoxim, Cefotaxim und HR 221 wurde tierexperimentell untersucht. Tiermodell war die experimentelle östrogengebahnte und nicht-gebahnte chronischeE. coli-Pyelonephritis der Ratte. Die Tiere wurden für eine Woche 2× täglich mit 5 mg Cephalosporin/kg behandelt. Alle Cephalosporine führten zu einem signifikanten Abfall der renalen Keimzahlen trotz der niedrigen Dosierung. In beiden Tiermodellen war Ceftazidim signifikant wirksamer als HR 221, obwohl die Serumspiegel von HR 221 höher waren und länger andauerten als die von Ceftazidim. Unterschiede in der Pharmakokinetik (metabolische Stabilität, Proteinbindung) könnten der Grund für die unterschiedliche therapeutische Effektivität sein, da die antimikrobielleIn-vitro-Aktivität aller Cephalosporine gegenüber dem Testkeim sehr ähnlich war.
    Notes: Summary The therapeutic efficacy and pharmacokinetics of the cephalosporins ceftazidime, ceftizoxime, cefotaxime and HR 221 were studied in animal experiments. The animal model used was experimental estrogen-induced or non-induced chronicEscherichia coli pyelonephritis in rats. The animals were treated with 5 mg cephalosporin/kg twice daily for one week. Each of the cephalosporins tested led to a significant decrease in renal bacterial counts, in spite of the low doses given. Ceftazidime was significantly more active than HR 221 in both experimental models, although the serum levels of HR 221 were higher and were maintained for a longer period of time than those of ceftazidime. Differences in pharmacokinetic properties (influenced by metabolic stability and protein binding) could be the reason for the differences in therapeutic activity, since thein vitro antimicrobial activity of each of the cephalosporins tested was very similar against the test strain.
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  • 3
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Es wurde der Einfluß von D-Glukaro-1,5-Laktam auf die Aminoglykosid-induzierte Nephrotoxizität tierexperimentell an der Ratte untersucht. Parameter der Nephrotoxizität waren die Ausscheidung von Tubuluszellen und Malat-Dehydrogenase im Harn. Wenn D-Glukaro-1,5-Laktam in geeigneter Dosis entweder intramuskulär oder peroral gegeben wurde, reduzierte sich die Exkretion von Zellen und Enzymen während der Verabreichung von Gentamicin, Tobramycin, Dibekacin, Netilmicin und Ribostamycin signifikant. D-Glukaro-1,5-Laktam verminderte nicht die therapeutische Effektivität von Ribostamycin in der experimentellen Chemotherapie der akuten Pyelonephritis der Ratte. Der Schutzeffekt von D-Glukaro-1,5-Laktam könnte der Hemmung der Beta-Glukuronidase, einem Enzym, das sich in renalen Lysosomen befindet und von Aminoglykosiden aktiviert wird, zugeschrieben werden.
    Notes: Summary We studied the effect of D-glucaro-1,5-lactam on aminoglycoside-induced nephrotoxicity in rats. Parameters of nephrotoxicity were urinary excretion of tubule cells and malate dehydrogenase. When given in appropriate doses, either i. m. or via an oral tube, D-glucaro-1,5-lactam significantly reduced the excretion of cells and enzymes during the administration of gentamicin, tobramycin, dibekacin, netilmicin and ribostamycin. It did inot impair the therapeutic efficacy of ribostamycin in the experimental treatment of acute pyelonephritis in rats. The protective effect of D-glucaro-1,5-lactam could be ascribed to its inhibition of β-glucuronidase, an enzyme which is located in renal lysosomes and which is activated by aminoglycosides.
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