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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
    ISSN: 1573-904X
    Keywords: drug delivery system ; biomaterials ; self-setting bioactive carbonate apatite cement ; in vitro indomethacin release ; mercury porosimetry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. In the present study, to develop a drug delivery system with higher bioacitivity in hard tissues by using the self-setting bioactive carbonate apatite cement, we have investigated the effects of sodium bicarbonate content on thein vitro drug release from a self-setting bioactive carbonate apatite cement containing indomethacin (IMC). Methods. The cement powder systems constituted an equimolar mixture of tetracalcium phosphate (Ca4(PO4)2O) and dicalcium phosphate dihydrate (CaHPO4⋅2H2O), hydroxyapatite (HAP, Ca10(PO4)6(OH)2) seed crystals and sodium bicarbonate. Two types of 2% IMC loaded-cements were prepared as follows, one containing 0% HAP seed crystal and 0−10% sodium bicarbonate, and the other containing 40% HAP seed crystal and 0−10% sodium bicarbonate. The drug release profiles from 2% IMC loaded-cements were measured in simulated body fluid at pH 7.25 and 37.0°C. Results. The drug release profiles from the cement matrix systems with or without seed crystals were estimated using a moment analysis computer program. The mean drug release time (MDT) and the time required for 50% drug release of the cement containing 0 and 40% seed crystal decreased with an increase of sodium bicarbonate. Furthermore, after the drug release the total pore volume of the cement matrix, as measured by mercury porosimetry, increased with an increase of sodium bicarbonate. Conclusions. MDT and T50's were a function of adding the amount of sodium bicarbonate. The results of the relationship between the micropore distribution, total volume of pores after drug release and drug release supported the hypothesis that the variation in drug release from the cements resulting from the addition of sodium bicarbonate was mainly due to an increase in the diffusion of the drug in the micropores of the cement by dissolution or erosion of the cement matrix.
    Type of Medium: Electronic Resource
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