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Parameter estimability of biphasic response models

S Dutta1, W F Ebling

  • 1Department of Pharmaceutics, State University of New York at Buffalo, Amherst, NY 14260, USA.

Journal of Pharmaceutical Sciences
|January 1, 1997
PubMed
Summary
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General anesthetic pharmacodynamics show biphasic effects. Data descriptors accurately summarize concentration-effect relationships, even when model parameters are poorly estimated.

Area of Science:

  • Pharmacology
  • Pharmacodynamics
  • Anesthesiology

Background:

  • General anesthetic agents often display biphasic concentration-effect relationships, involving activation at low and inhibition at high concentrations.
  • These relationships are typically modeled using modifications of the nonlinear sigmoid E(MAX) model.

Purpose of the Study:

  • To assess the parameter estimability of simple additive biphasic pharmacodynamic models using Monte Carlo simulations.
  • To compare the accuracy and precision of estimated model parameters and data descriptors against true values.

Main Methods:

  • Employed Monte Carlo simulations to test and quantify parameter estimability in biphasic pharmacodynamic models.
  • Calculated concentration-effect data descriptors from estimated model parameters.

Related Experiment Videos

  • Compared estimated parameters and descriptors to their known true values.

    • Main Results:

    • When the IC50/EC50 ratio was low (<10), E(MAX), EC50, and IC50 parameters showed poor estimation (high bias and coefficient of variation).
    • Despite poor parameter estimation, model fits were excellent, and calculated data descriptors were precise and accurate.
    • Data descriptors demonstrated superior estimability compared to model parameters, especially when the IC50/EC50 ratio increased.

    Conclusions:

    • Data descriptors offer a more reliable method for summarizing anesthetic concentration-effect relationships than model parameters, particularly when parameter separation is limited.
    • Model parameter estimability improves with greater separation between EC50 and IC50, leading to observable peak effect plateaus.