Multiple compartment indirect response models (top panel) and signature profiles for Models V and VI (bottom panel). Response curves were simulated using Eqs. 11 and 12 driven by drug concentrations following monoexponential disposition: Cp = Coe(−kt). Co was set to 10, 100, or 1,000 units to achieve increasing doses. Parameter values were k = 0.12/h, Imax = 1 unit, Smax = 10 units, EC50 = 15 units, ko = 25 unit/h, kp = 0.5/h, and kout = 0.25/h.