Table 2.
Overview of the composition of PK/PD models used for modeling of hemodynamic parameters in preclinical species and human, indicating selected concentration–effect relationship, model for capturing of potential time delays and baseline function
| Variable | Species | Concentration–effect relationship | Baseline function | Time delay |
|---|---|---|---|---|
| BP (including models of MAP, SBP, and DBP) | Human | Linear: eprosartan,43 prazasin,44 trimazosin,44 doxazosin,44,45 E708046 Emax: moxonidine,47 fimasartan,48 Emax sigmoidal: Remifentanil49 |
Constant: Remifentanil,49 prazasin,44 trimazosin,44 doxazosin,44,45 E7080,46 nifedipine50 2x cosine function: eprosartan,43 fimasartan,48 moxonidine47 |
Effect compartment: Remifentanil,49 eprosartan,43 prazasin,44 trimazosin,44 doxazosin44,45 IDR: E7080,46: fimasartan48 |
| BP (including models of MAP, SBP, and DBP) | Rat | Linear: milrinone51 Log-linear: metabolites52 Emax/Imax: L-NAME,51 doxazosin51 Sigmoidal Emax: IIDN,52 IMDN,52 ISDN52 |
Constant: IIDN,52 IMDN,52 ISDN52 Sällström baseline53: L-NAME,51 milrinone,51 doxazosin51 |
IDR: L-NAME,51 milrinone51 |
| BP (including models of MAP, SBP, and DBP) | Guinea pig | Emax/Imax: milrinone,51 Doxazosin,51 L-NAME51 |
Linear: L-NAME,51 milrinone,51 doxazosin51 | IDR: milrinone51 |
| BP (including models of MAP, SBP, and DBP) | Dog | Linear: milrinone,51 Compound 12,31 doxazosin51 Emax/Imax: L-NAME51 |
Constant: Compound 1231 Cosine function: L-NAME,51 milrinone,51 doxazosin51 |
IDR: L-NAME,51 milrinone,51 Compound 1231 |
| HR | Human | Linear: PF-0082138554 Emax/Imax: PF-00610355,55 cilobradine56 |
Negative Gaussian function: PF-0061035555 Indirect periodic function with exercise: cilobradine56 Cosine function: PF-0082138554 |
Effect compartment: PF-0061035555 Transduction: cilobradine56 |
| HR | Rat | Linear: milrinone51 Emax/Imax: L-NAME,51 doxazosin51 Operational model of agonism: CPA57 |
Constant: CPA57 Sällström baseline53: L-NAME,51 milrinone,51 doxazosin51 |
IDR: L-NAME,51 doxazosin,51 milrinone51 |
| HR | Guinea pig | Emax/Imax: milrinone,51 doxazosin51 L-NAME51 | Linear: L-NAME,51 milrinone,51 doxazosin51 | IDR: milrinone,51 doxazosin51 |
| HR | Dog | Linear: milrinone,51 PF-0082138554 doxazosin51 Threshold linear: Compound 10,31 Emax/Imax: L-NAME51 |
Cosine function: L-NAME,51 milrinone,51 doxazosin,51 PF-0082138554 | IDR: L-NAME,51 milrinone51 |
| dP/dt max | Dog | Linear: Compound 1131 | Constant: Compound 1131 | IDR: Compound 1131 |
References contained in Supplementary Material. IDR, indirect response model.