Binding affinity of purified plasma proteins for phenethylbiguanide, an oral hypoglycemic compound.

IN AN EVALUATION of approximately 200 new monoand disubstituted derivatives of formamidinyliminoureas, Ungar (1) found that phenethylbiguanide or N ‘-beta-phenethylformadinyliminourea hydrochloride was a highly active oral hypoglycemic agent in both normal and alloxan-diabetic animals of five different species. Subsequent clinical investigations by Pomeranze (2) on 54 diabetic patients in all age groups and of all degrees of severity of their disease showed an effect on glycemia and glycosuria in all patients who tolerated the drug in sufficient dosage. Krall (3) has likewise reported favorable results for phenethylbiguanide as a hypoglycemic agent in 65 per cent of the patients studied. About 15 per cent of the remaining patients responded to the drug but treatment was discontinued because of adverse gastrointestinal side effects. In another 10 per cent of cases the doses were insufficient to produce hypoglycemia because of the side effects that appeared before effective blood levels of the drug had been reached. From studies of protein interactions it is apparent that drugs bound by plasma proteins are pharmacologically inactive and in this respect the proteins can act as a drug “buffer” (4). By decreasing