Overview of input, data features, model, parameters, observations, and references for the case studies
| No. | Case Study | Input | Features of Data | Model | Parameter | Reference |
|---|---|---|---|---|---|---|
| 1 | Tail flick | i.v. (3 and 10 µg), s.c. (10, 50, and 100 µg) | Baseline, peak shift, saturation, absorption rate–limited duration of response | Bolus and first-order input/output biophase coupled to a turnover response model | F, Ka, K, kin, kout, SD50, Smax, nH | Gabrielsson et al. (2000) |
| 2 | Locomotor activity stimulation | s.c. (3.12 and 5.82 µg/kg) | No baseline, peak shift, zero-order rise and decline of response, saturation of build-up and loss | First-order input/output biophase coupled to a turnover response model | K’, kout, kM, SD50, Smax, nH | van Rossum and van Koppen (1968) |
| 3 | Fatty acid response | Multiple i.v. infusions plus washout | Baseline, saturation, rebound, tolerance | Zero-order input and first-order loss biophase model coupled to a turnover feedback model | K, R0, kout, ktol, ID50, nH | Gabrielsson and Peletier (2008), Isaksson et al. (2009) |
| 4 | Psychosis score (BPRS) | 120–600 mg daily p.o. dosing | Baseline, time to PD steady state, subcategorizing responders | Constant biophase exposure coupled to a turnover model | kin, kout, Imax | Lewander et al. (1990), Gabrielsson and Weiner, (2016) |
| 5 | Bacterial growth and kill | Multiple i.v. doses | Baseline, growth limit, saturation | First-order growth and second-order kill rate | kg, kk | Gabrielsson and Weiner (2010) |
| 6 | Cortisol release during and after exposure to ACTH | Experimental model of ACTH exposure driving the release rate of cortisol | Baseline, rebound, tolerance turnover, endogenous agonist, square wave of ACTH | Square-wave exposure to the endogenous agonist ACTH coupled to a turnover feedback model of cortisol release rate | kin, kout, SD50, Smax, nH | Urquhart and Li (1968), Gabrielsson and Weiner (2010) |
| 7 | Miotic response in the cat eye | Three doses (0.1, 1.0, and 10 µg latanoprost) given topically | Baseline, partial inhibition, saturation, rapid equilibrium model | Inhibitory Emax model | Ka, K, tlag, ID50, Imax, nH | Smolen (1971a), Gabrielsson et al. (2000) |
| 8 | Meta-analysis of fatty acid and insulin response to multiple NiAc provocations (NLME analysis) | Multiple i.v. and s.c. doses, rates, and modes of NiAc plus washout | Baseline, saturation, rebound, tolerance turnover, multiple biomarkers, multiple drug provocations, endogenous agonist, input-stimulated washout profile | Saturable input-output biophase model of endogenous agonists coupled to a turnover feedback model of FFA and insulin in normal and diseased animals | KaM, Vmax, K, kin, kout, SD50, Smax, nH | Isaksson et al. (2009), Andersson et al. (2016, 2017) |
NLME, nonlinear mixed effects; PD, pharmacodynamic.