STEADY-STATE PHARMACOKINETICS OF METHADONE IN OPIOID ADDICTS

Kinetic parameters were investigated in tolerant methadone maintenance patients. The disposition of methadone at steady-state was assessed on 8 occasions - in 5 opioid addicts prescribed wide ranging doses of methadone (10 mg to 60 mg per day) - providing unique pharmacokinetic data. Statistical analysis showed that the kinetics of oral methadone at steady-state were described using a single compartment model. Analysis of the plasma concentration-time curves gave estimates of the variance of methadone clearance and apparent volume of distribution, and indicate that methadone is rapidly absorbed (mean K(a), 1.7 h-1) with a detectable increase in the plasma drug concentration 15 to 30 min after dosing. The elimination of methadone from plasma was found to occur slowly (mean t1/2 26.8 h) beginning soon after the administration of the daily oral prescription. The apparent volume of distribution - assuming the oral bioavailability (f) of methadone to be 0.95 - was large (mean 6.71 . kg-1). The slow clearance of this drug from the body (mean 3.1 ml . min-1 . kg-1) confirms that daily dosing at steady-state is adequate to maintain effective plasma concentrations throughout the dosing interval.