THE PHYSIOLOGICAL DISPOSITIONS OF BIPHENYL DIMETHYL-DICARBOXYLATE(BDD)

Dimethyl-4, 4'-dimethoxy-5,6,5',6'-dimethylenedioxy-biphenyl-2, 2'-dicarboxylate. (Biphenyl dimethyl-dicarboxylate, BDD) is an intermediate for the synthesis of schizandrin C analogs. BDD was shown to have SGPT-lowering action in mice intoxicated with CCl₄ or thioacetamide and protective action on liver injury induced by CCl₄. Clinical trial showed that BDD was effective in lowering SGPT in patients with chronic hepatitis and no toxic effect was observed.In this paper, the absorption, distribution, metabolism and excretion of BDD in mice, rats and the excretion of the drug in man were studied by using tritium labeled BDD and by HPLC.After oral administration of ³H-BDD to rats, the plasma radioactivity reached maximum level in about 12 h and leveled off slowly. However, of the total radioactivity only a very small fraction was shown to be unchanged drug. The levels of radioactivity in all tissues were higher at 12 h than at 4 or 24 h after drug administration. Highest level of radioactivity was found in the liver. When cold BDD was administered to rats, however, nearly nounchanged drug was detected in the serum and tissues by the HPLC method.After intravenous injection of cold BDD to rats, the blood level was found to decrease in two phases, the distribution phase andthe elimination phase, with T1/2 of 0.35 h and 5.7h, respectively. The apparent volume of distribution was found to be 3.44 1/kg. At 10 min Or 30 min after administration, highest level of BDD was found in liver, while after 5 h, the drug level in fat Was the highest.After oral administration, the amount of BDD excreted in feces was 70～80% of the administered dose for mice, rats and normal human. The gastroenteric absorption of the drug in rats was shown to be about 20%. After administration of 3~H-BDD to rats, 14.1% of the radioactivity was excreted in urine within 72 h and 5% of the radioactivity was excreted in bile in 24 h. However, nearly no unchanged drug was foundin the urine and bile. The radioactivity in the urine and bile was shown to be wa ter soluble metabolites.Incubation studies with tissue slices in vitro showed that BDD was metabolized rapidly by liver, but not by kidney, lung or whole blood. It appears that there is a first pass effect when BDD is administered orally.