modelPKPD_Midazolam
Extends from Examples.PK_2C_IVMidazolam.
Information
The pharmacodynamic components outputs the effect based on concentration in target tissue. An example of PKPD model of Midazolam where pharmacokinetic part is modeled using 2-compartment model and central compartment is connected to sigmoid effect component.
Simulation of effect of the drug on EEG activity is fitted to reference data published at (Cleton, Voskuyl, and Danhof 1998).
References:
Cleton, A, R A Voskuyl, and M Danhof (1998-10). “Adaptive changes in the pharmacodynamics of midazolam in different experimental models of epilepsy: kindling, cortical stimulation and genetic absence epilepsy: Epilepsy induced reduction in midazolam efficacy”. en. In: Br. J. Pharmacol. 125.4,pp. 615–620. ISSN: 0007-1188,1476-5381. DOI: 10.1038/sj.bjp.0702088. URL: http://dx.doi.org/10.1038/sj.bjp.0702088
Parameters
| Type | Name | Default | Description |
|---|---|---|---|
| Pharmacolibrary.Types.MassConcentration | Cmin (from PK_2C_IVMidazolam) | 6.3e-5 | |
| Pharmacolibrary.Types.MassConcentration | Cmax (from PK_2C_IVMidazolam) | 3e-4 | |
| Modelica.Units.SI.Time | dataTimeScale | 7.7 | Translation from rat to man |
Components
| Type | Name | Default | Description |
|---|---|---|---|
| Pharmacolibrary.Sources.PeriodicDose | periodicDose (from PKTwoCompartmentModel) | ||
| Pharmacolibrary.Pharmacokinetic.NoPerfusedTissueCompartment | peripheral (from PKTwoCompartmentModel) | ||
| Pharmacolibrary.Pharmacokinetic.NoPerfusedTissueCompartment | central (from PKTwoCompartmentModel) | ||
| Pharmacokinetic.ClearanceDrivenElimination | elim (from PKTwoCompartmentModel) | ||
| Pharmacokinetic.TransferFirstOrderNonSym | transfer (from PKTwoCompartmentModel) | ||
| Modelica.Blocks.Sources.CombiTimeTable | CTT_MidazolamC (from PK_2C_IVMidazolam) | This is a validation from literature | |
| Pharmacodynamic.SigmoidEmaxEffect | PD_Midazolam | ||
| Modelica.Blocks.Sources.CombiTimeTable | CTT_MidazolamEffect_Epileptic | EEG values are showing Midazolam effect. Data from literature [7], figure 2A epileptic |
Revisions
- 05/2025 Tomas Kulhanek, initial model
- 05/2025 Filip Jezek, experimental data fit to model