Acute i.v. Methadone Kinetics in Man: relationship to chronic studies

Twenty-six patients were given methadone 10 mg i.v. to obtain acute human kinetics. Plasma methadone concentrations from separate 3- and 6-h studies were measured by radioimmunoassay. Kinetic parameters derived from triexponential NONLIN analysis showed that T1/2 alpha and T1/2 beta were 2 and 30 min respectively; no reliable estimate for T1/2 gamma could be obtained. The clearance was estimated as 149 /+- 62 and 163 /+- 49 ml min-1 in the 3- and 6-h studies respectively. These values are compared with those published for chronic administration. The difficulties in determining accurate terminal half-life and clearance values from short duration studies are discussed; these difficulties are accentuated by the long terminal half-life of methadone. Appropriate estimates of clearance may be derived from an acute short duration study provided that the average of triexponential fits to individual patients data is used, even when data extend from only 3h. As might be anticipated, no analysis produced appropriate terminal half-life values for this drug.