Biopharmaceutical Study of the Hepato-biliary Transport of Drugs. V. Hepatic Uptake and Biliary Excretion of Organic Cations

The hepato-biliary transport characteristics in vivo and the uptake process by liver slices and by liver cell suspensions were studied in rats using procaineamide ethobromide, its N-acetyl compound and quinine. These organic cations were transported from plasma to liver and from plasma to bile against a concentration gradient, and their biliary excretion was depressed by an administration of the other organic cations in accordance with earlier studies. However the hepatic uptake of quinine was extremely high, 39 of the liver/plasma concentration ratio, as compared with 8.6 of PAEB and 1.7 of APAEB. When taken up by liver slices or liver cell suspensions, PAEB and quinine showed completely different patterns. Slice/medium ratio of PAEB obtained by liver slices attained 3.6 after 4 hours and cell/medium ratio obtained by liver cell suspensions did not attain one. On the other hand, slice/medium and cell/medium ratios of quinine attained about 20 and the high slice/medium ratio was only slightly decreased in an atmosphere of nitrogen or in the presence of DNP. The hepatic high uptake of quinine observed both in vivo and in vitro is mostly explainable by lipid-binding mechanism as the binding to liver lipids showed quite a high value, 77%.