RELATIONSHIP BETWEEN PHARMACOKINETICS AND PHARMACODYNAMIC ACTION AS APPLIED TO INVIVO PA2 - APPLICATION TO ANALGESIC EFFECT OF MORPHINE

  • 1 January 1978
    • journal article
    • research article
    • Vol. 206  (1) , 38-45
Abstract
When the pA2 [effective concentration of agonist to antagonist] of an antagonist was determined in vivo, administered doses were used rather than the peak or steady-state tissue concentrations. The error which can arise in this method and also a method for determining the pA2 from data obtained at times after peak was presented. This time-dependent analysis to time-dose-response data was obtained with morphine-naloxone in the rat, using tail compression as the nociceptive stimulus. Good agreement between pA2 values was found: 8.0 with peak effect data and 8.1 with the time-dependent method. Further, this analysis yielded 20 min as the half-life of naloxone. The time-dependent method provided a check on the pA2 in vivo and confirmed the utility of this constant in classifying receptors. The appendix contained methodology for application to other agonist-antagonist combinations classified according to their kinetics.

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