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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 355-368 
    ISSN: 1573-8744
    Keywords: bumetanide ; indomethacin ; effect-compartment model ; dose-response relationship
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Analyses of bumetanide's dose-response relationship have been complicated by the hysteresis observed between the drug's urinary excretion rate and its sodium excretion. This apparent time lag reflects the disequilibrium between the urine concentration and effect compartment (biophase) which occurs during the early distribution phase. In the present article, an expanded pharmaco-dynamic model has been introduced in which the hypothetical effect compartment is linked, by a first-order process (Kue),to the urine compartment. Drug dissipation from the effect compartment occurs by means of the first-order rate constant, Keo.This representation accommodates bumetanide's luminal site of action in the kidney tubule as well as the drug's temporal component. Application of this model to the bumetanide-indomethacin interaction in dogs is examined.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 31-46 
    ISSN: 1573-8744
    Keywords: bumetanide ; probenedd ; pharmacokinetics ; pharmacodynamics ; doseresponse relationship
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics and pharmacodynamics of intravenous bumetanide (0.250 mg/kg), alone (treatment I) and after probenecid pretreatment (treatment II), were studied in four mongrel dogs. Lactated Ringer's solution was administered by vein throughout both treatments at a flow rate of 2 ml/min to avoid fluid and electrolyte depletion. Bumetanide and probenecid concentrations were analyzed by HPLC, sodium by flame photometry, and creatinine by colorimetry. Although the probenecid markedly reduced the plasma and renal clearances of bumetanide, as well as the fraction excreted unchanged in the urine, there was no significant difference between treatments I and II in the 4-hr natriuretic and diuretic responses. However, analysis of the dose-response curves between treatments I and II showed that sodium, excretion was better correlated with bumetanide urinary excretion rate than with plasma concentration. The reasons for a poor correlation between treatments during the early time periods are discussed.
    Type of Medium: Electronic Resource
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