Tissue Distribution of Methadone Following Percutaneous Absorption in Vivo

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Abstract
Using the intact hairless mouse as an experimental model for human skin, the relative distribution of methadone in blood, brain, heart, liver, and lung was studied hourly for 4 hr following percutaneous absorption of the hydrochloride salt in aqueous solution. The resulting tissue distribution was compared with that observed following administration of the drug by intraperitoneal injection. With percutaneous absorption the mean tissue concentrations of methadone generally increased with time, presumably due to sustained administration of the compound. Blood concentrations were similar to those observed after oral administration of pharmacologic doses of methadone to humans. By 4 hr the mean methadone concentration in blood was higher with percutaneous absorption than with intraperitoneal injection. However, in all other instances mean tissue concentrations for each hour were higher following intraperitoneal injection of methadone. Per cutaneous absorption may prove to be a potentially effective route for continuous slow administration of methadone hydrochloride.