Overview of in vivo drug response phases, features of data, parameters, and case studies

PhaseFeatures in DataParameterCase Study
A: baselineStable, variable, oscillating, or drifting (e.g., due to disease)R0, kin, kout1, 2–8
B: time delayTime delay between expected plasma peak concentration and peak of responsekout, K, Ka1–6
C: onset of actionConcave or convex rise of response (onset of action); overshoot during onsetkout, K, Ka, number of transit compartments, ktol1–7
D: peak shiftPeak shift or not; a shift suggests a nonlinear stimulation/inhibition of actionSmax/Imax, SD50/ID50, n1–6, 8
E: response maximum or minimumMay indicate a nonlinear drug action or physiologic limit; the same with an inhibitory drug actionSmax/Imax, SD50/ID50, n, physiologic limit1–5, 7, 8
F: return to baselineDifferent dose routes may reveal absorption rate–limited elimination of drug from biophase; rebound during washoutkout, K, Ka, ktol1–3, 5–8