• Pharmaceutical research · Dec 1994

    The use of multiple doses and pharmacodynamic system analysis to distinguish between dispositional delays and time-variant pharmacodynamics.

    • M R Gastonguay and S L Schwartz.
    • Department of Pharmacology, Georgetown University School of Medicine, Washington, D.C. 20007.
    • Pharm. Res. 1994 Dec 1; 11 (12): 1825-8.

    AbstractPharmacokinetic-pharmacodynamic modeling algorithms, in general, rely on hysteresis minimization techniques that assume time-invariant pharmacodynamics (constant biophase concentration-effect relationships). When time-variant pharmacodynamics are observed, a specific model for tolerance or sensitization is required. However, with single dosing, hysteresis that results from a time-variant biophase concentration-effect relationship cannot be distinguished from hysteresis caused by dispositional delays. This can lead to the inappropriate minimization of hysteresis. As an approach to this problem, simulated and real kinetic-dynamic data were analyzed with the pharmacodynamic system analysis program ATTRACT. The use of a multiple dosing regimen and this hysteresis minimization algorithm resulted in a simple diagnostic test to distinguish between dispositional effects of acute tolerance and sensitization.

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