TABLE 2

Overview of input, data features, model, parameters, observations, and references for the case studies

No.Case StudyInputFeatures of DataModelParameterReference
1Tail flicki.v. (3 and 10 µg), s.c. (10, 50, and 100 µg)Baseline, peak shift, saturation, absorption rate–limited duration of responseBolus and first-order input/output biophase coupled to a turnover response modelF, Ka, K, kin, kout, SD50, Smax, nHGabrielsson et al. (2000)
2Locomotor activity stimulations.c. (3.12 and 5.82 µg/kg)No baseline, peak shift, zero-order rise and decline of response, saturation of build-up and lossFirst-order input/output biophase coupled to a turnover response modelK’, kout, kM, SD50, Smax, nHvan Rossum and van Koppen (1968)
3Fatty acid responseMultiple i.v. infusions washoutBaseline, saturation, rebound, toleranceZero-order input and first-order loss biophase model coupled to a turnover back modelK, R0, kout, ktol, ID50, nHGabrielsson and Peletier (2008), Isaksson et al. (2009)
4Psychosis score (BPRS)120–600 mg daily p.o. dosingBaseline, time to PD steady state, subcategorizing respondersConstant biophase exposure coupled to a turnover modelkin, kout, ImaxLewander et al. (1990), Gabrielsson and Weiner, (2016)
5Bacterial growth and killMultiple i.v. dosesBaseline, growth limit, saturationFirst-order growth and second-order kill ratekg, kkGabrielsson and Weiner (2010)
6Cortisol release during and after exposure to ACTHExperimental model of ACTH exposure driving the release rate of cortisolBaseline, rebound, tolerance turnover, endogenous agonist, square wave of ACTHSquare-wave exposure to the endogenous agonist ACTH coupled to a turnover back model of cortisol release ratekin, kout, SD50, Smax, nHUrquhart and Li (1968), Gabrielsson and Weiner (2010)
7Miotic response in the cat eyeThree doses (0.1, 1.0, and 10 µg latanoprost) given topicallyBaseline, partial inhibition, saturation, rapid equilibrium modelInhibitory Emax modelKa, K, tlag, ID50, Imax, nHSmolen (1971a), Gabrielsson et al. (2000)
8Meta-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 washoutBaseline, saturation, rebound, tolerance turnover, multiple biomarkers, multiple drug provocations, endogenous agonist, input-stimulated washout profileSaturable input-output biophase model of endogenous agonists coupled to a turnover back model of FFA and insulin in normal and diseased animalsKaM, Vmax, K, kin, kout, SD50, Smax, nHIsaksson et al. (2009), Andeon et al. (2016, 2017)
  • NLME, nonlinear mixed effects; PD, pharmacodynamic.