Absence of metabolism of morphine during accumulation by isolated perfused rabbit lung.

Pulmonary accumulation and metabolism of morphine was studied in an isolated perfused lung system. No metabolism of morphine or N-demethylation of ethylmorphine was found. Accumulation from the recirculating perfusate was nonsaturable over a concentration range of 3-400 microM morphine. Inhibition of sodium transport or sodium depletion decreased morphine accumulation. The results are most consistent with passive diffusion of morphine down an electrochemical gradient and subsequent nonspecific binding to tissue anions. Normal movement of sodium and potassium is required to maintain this gradient.