Alcohol and the steady-state disposition kinetics of methadone in rats

In order to examine whether alcohol alters the steady-state disposition of chronic or acute doses of methadone, three groups (N = 5 each) of male Sprague-Dawley rats were administered oral doses of methadone daily for 14 days. Group 1 received oral doses of alcohol twice daily whereas groups 2 and 3 were given isocaloric sucrose. Water was provided ad libitum and food consumption was controlled by paired feeding. On day 15, all of the animals were given the last dose as C14 methadone. Group 2 received a concurrent dose of alcohol but groups 1 and 3 received isocaloric sucrose. Blood was drawn at timed intervals for 48 hr. Methadone and its major metabolite (M1) in plasma were separated by thin-layer chromatography and underwent liquid scintillation counting. The elimination half-life (t1/2, beta) and the area under the plasma concentration-time curve (AUC) of methadone and M1 were determined in all of the three groups. Group 1 demonstrated the smallest AUC and the shortest t1/2 for methadone and M1 (p less than .05). Group 2 displayed the highest amount of unchanged methadone (p less than .05) in the first 2 hr after administration, but its t1/2 and AUC of methadone and M1 were not significantly different from those of group 3. These data may help explain why there is a high incidence of heavy drinking among methadone-maintained patients.