Morphine binding to human plasma proteins

The interaction of (N-methyl-14C) morphine with purified human albumin and gamma globulin and with human plasma was studied by equilibrium dialysis. Morphine binds to albumin and, to a lesser extent, to gamma globulin, but probably does not bind to plasma lipoproteins. The per cent of drug bound to protein was dependent on protein concentration but independent of drug concentration in the therapeutic range of plasma morphine concentration. In this range, 34.0% to 37.5% of the drug is bound to human plasma, largely to the albumin fraction. This study is compared to an earlier one on the interaction of methadone with plasma proteins. It is likely that the lower lipid solubility of morphine compared to methadone is related to its decreased affinity for plasma proteins.