Fig. 8. Simulations using the pharmacokinetic–pharmacodynamic model of the analgesic effect (pain tolerance) in men (M, thin lines) and women (F, thick lines). (A ) Bolus dose of 0.1 mg/kg morphine at t = 0. Despite the lesser potency of morphine in men, the analgesic effect in men is initially greater because of the faster equilibration of morphine concentration between plasma and effect site. (B ) Bolus dose of 0.1 mg/kg morphine at t = 0 followed by 30 μg · kg−1· h−1for 1 h. The area under the curve is greater for women than men by a factor of 2. (C ) Simulations intended to obtain similar analgesic profiles (equal peak effects and area under the curves) in men and women using a regimen of a bolus dose plus patient-controlled analgesia. A 12.0-mg bolus dose was administered in men (weight = 75 kg) at t = 0, followed by 0.5-mg infusions at 10-min intervals throughout the 7-h simulation. A 15.4-mg bolus dose was administered in women (weight = 75 kg), followed by no morphine for 120 min and then subsequent 0.34-mg infusions at 20-min intervals for the remainder of the simulation. The total amount of morphine used during the 7-h simulation was 33.0 mg in men and 20.4 mg in women.
