Figure 2.

Relationship between methadone dose and duration of effect. Simulated methadone blood concentrations vs time are based on the pharmacokinetic parameters of Gourlay et al,¹⁸ as are the minimal effective analgesic methadone concentration (approximately 30 ng/ml), and the threshold for significant (5-6 breaths/min) respiratory depression (approximately 100 ng/ml).¹⁹ Data are shown for intravenous bolus methadone doses of 5, 10, 20 and 30 mg. Estimated duration of analgesia for these doses is approximately <0.5, <0.5, 24 and 36 hr. Duration of analgesia is governed by redistribution (and the redistribution half-life of approximately 5 min) for the 5 and 10 mg doses, but by elimination (and the elimination half-life of approximately 30 hr) for the larger doses. The inset shows plasma concentrations for the first hr after dosing. Due to rapid redistribution, anticipated respiratory depression would be less than 30-45 min, even at the higher single bolus doses.