Fig. 5. Simulation study. The effect of variations in opioid-agonist-related model parameters on 100 μg naloxone reversal at t = 55 min on 21 mg morphine-6-glucuronide (M6G)-induced respiratory depression at t = 0. The red line is the simulation with the parameter value = 20% of the typical population value for M6G (table 4), green line = 50%, blue line = 100%, purple line = 200%, and yellow line = 500%. (A ) M6G t½ke0, (B ) M6G kon, (C ) M6G koff, and (D ) koffand konat a fixed ratio such that Kd(koff/kon) = constant. konand koff= receptor equilibration constants for ligand receptor association and dissociation, respectively, t½ke0= blood-effect-site equilibration half-life.