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  • 1
    ISSN: 1573-904X
    Keywords: microdialysis ; methods ; theophylline ; pharmacokinetics ; rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Three microdialysis methods, the “tritium” method, the “point-of-no-net-flux” method, and a method using the low perfusion rate of 0.1 µl/min, were compared with respect to their ability to generate estimates of unbound steady-state concentrations (Cuss) of the antiasthmatic drug theophylline in blood and brain tissue in anesthetized rats. Concomitantly, the influence of the perfusion flow rate on the estimated extracellular Cuss obtained with the point-of-no-net-flux method was investigated. Theophylline was administered as a rapid intravenous bolus dose followed by constant intravenous infusion. Changes in perfusion flow rate from 2.0 to 0.75 µl/min and, finally, to 0.25 µl/min, using the point-of-no-net-flux method, had no significant effect on the estimated Cuss of theophylline in blood and striatum. This observation, particularly in the case of brain tissue, is not consistent with the theory that the process of dialysis drains a significant amount of substance from the immediate vicinity of the dialysis probe. Similar estimates of Cuss in blood as well as in brain tissue were obtained with all three methods. Their accuracy in estimating Cuss in blood was further strengthened by observations of unbound fractions similar to those reported in the literature. Furthermore, all three methods gave striatum/blood ratios at steady state of approximately 0.5, indicating that there is active transport of theophylline from brain tissue. It is concluded that the tritium method, when validated, can be used to study the time course of unbound drug concentrations in blood and tissues.
    Type of Medium: Electronic Resource
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