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Comparison of four basic models of indirect pharmacodynamic responses
N L Dayneka1, V Garg, W J Jusko
1Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo 14260.
Journal of Pharmacokinetics and Biopharmaceutics
|August 1, 1993
Summary
Four indirect pharmacodynamic models were compared, revealing that drug concentrations precede responses and model parameters can be biologically implausible. These indirect models differ from direct pharmacodynamic models.
Area of Science:
- Pharmacology
- Pharmacodynamics
- Pharmacokinetics
Background:
- Characterizing indirect pharmacodynamic responses is crucial for understanding drug action.
- Existing models often assume direct drug effects, which may not always apply.
Purpose of the Study:
- To develop and compare four basic models for indirect pharmacodynamic responses.
- To evaluate the behavior of these models using simulations.
Main Methods:
- Developed four indirect pharmacodynamic models based on drug effects on response input or dissipation.
- Utilized pharmacokinetic parameters of methylprednisolone for computer simulations.
- Generated plasma concentration and response-time profiles.
Main Results:
- Simulated responses exhibited slow onset and slow return to baseline.
- Time to maximal response varied with model and drug dose.
- Hysteresis plots indicated drug concentrations preceded responses.
- Fitting responses to direct pharmacodynamic models yielded dose-dependent and biologically implausible parameters.
Conclusions:
- Indirect pharmacodynamic models are distinct from conventional direct models.
- The developed models offer a framework for analyzing pharmacologic effects.
- Understanding indirect response mechanisms is essential for accurate drug effect evaluation.