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 Ka, 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 6.7 l.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.
Wolff
K
K
Department of Chemical Pathology, Old Medical School, University of Leeds, UK.
Hay
A W
AW
Raistrick
D
D
Calvert
R
R
D000328:Adult; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008691:Methadone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009293:Opioid-Related Disorders / Q000378:metabolism*
D008691:Methadone