The roles of P-glycoprotein and intracellullar metabolism in the intestinal absorption of methadone: in vitro studies using the rat everted intestinal sac

Methadone is used as a treatment for opiate detoxification in methadone mai ntenance programs. Intra- and inter-patient variations in methadone bioavai lability have been observed after oral methadone treatment and this makes i t difficult to predict a dosing regimen. Intestinal absorption and metaboli sm could explain these variations. The in vitro gut sac model was used to s tudy the intestinal absorption of methadone, and it confirmed that methadon e is a substrate for P-glycoprotein. The transport of methadone was increas ed in presence of P-gp inhibitors verapamil and quinidine. The appearance o f a major metabolite of methadone, 2-ethylidene-1, 5-dimethyl-3, 3-diphenyl pyrrolidine (EDDP) in the gut sac contents also demonstrated the existence of intestinal metabolism of methadone.