In the rat, the opiate effects produced by methadone are of short duration. For example, following 1.5 mg/kg iv tail flick latency ('analgesia') lasts for 100 to 150 minutes. Harris et al. (Fed. Proc. 37:470, 1978) report difficulty in demonstrating the development of physical dependence in methadone treated rats. We have measured plasma methadone levels using an RIA method developed in this laboratory together with 'analgesia' in male rats prepared with chronic catheters. After rapid iv dosing (1.5 mg/kg) the plasma methadone level over time data can be described by a two compartment open model with a t 1/2 β for methadone of approximately 60 min. The rapid elimination of methadone was confirmed in studies utilizing the continuous iv infusion of methadone for 6 hours followed by a washout period. In these studies the plasma clearance at steady state is equal to 83.3 ± 7.9 ml/min/kg, while the t 1/2 is 68.2 ± 0.4 minutes. The efficient clearance of methadone predicts a significant 'first pass effect' for oral methadone in this species. The pharmacokinetics of methadone in the rat may, in part, explain the time-action of opiate effects and variability in response seen after acute and chronic dosing with methadone.
|Original language||English (US)|
|Pages (from-to)||No. 1892|
|Issue number||3 I|
|State||Published - Jan 1 1979|
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