GLUTATHIONE S-TRANSFERASES AS A CEFPIRAMIDE BINDING-PROTEIN IN RAT-LIVER

To clarify the intrahepatical transport mechanism of cefpiramide, we i nvestigated effects of various agents mainly excreted into the bile by several different mechanisms on the biliary excretion of cefpiramide in rats. Sulfobromophthalein, indocyanine green, bilirubin and probene cid, known to be bound to glutathione S-transferases (GST) (EC 2.5.1.1 8) in liver cytosol, reduced the biliary excretion of cefpiramide, whi le neither secretory IgA, which is transported via vesicles in the liv er, nor colchicine, which inhibits movements of vesicles, had any effe ct on the excretion of cefpiramide. Propranolol and metoprolol, metabo lized by mixed function oxidases, had no effect on the biliary excreti on of cefpiramide. In the chromatography of liver cytosol, the amount of sulfobromophthalein or benzylpenicillin bound to the GST fraction d ecreased in the presence of cefpiramide or probenecid. The study showe d that cefpiramide was transported in the liver without relation to mi xed function oxidases or vesichle-mediated transporting system, but in relation to GST which binds cefpiramide, sulfobromophthalein, benzylp enicillin and probenecid, indicating an important role of GST in the c efpiramide excretion into the bile.