ACUTE I.V. METHADONE KINETICS IN MAN: RELATIONSHIP TO CHRONIC STUDIES

Abstract

Patients (26) were given methadone [an analgesic] 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. [initial phase, elimination, and terminal half-lives, respectively] could be obtained. The clearance was estimated as 149 .+-. 62 and 163 .+-. 49 ml/min in the 3- and 6-h studies, respectively. These values were compared with those for chronic administration. The difficulites in determining accurate t1/2.gamma. and clearance values from short-duration studies are discussed; these difficulties are accentuated by the long t1/2.gamma. of methadone. Appropriate estimates of clearance may be derived from an acute short duration study provided that the average of triexponential fits to individual patient data is used, even when data extend for only 3 h. As might be anticipated, no analysis produced appropriate t1/2.gamma. values for this drug.