Biopharmaceutical Study of the Hepato-biliary Transport of Drugs. VIII. Investigation of Hepatic Uptake of Organic Cations by Portal Infusion

The liver/plasma (L/P) ratios of acetyl procainamide ethobromide (APAEB), procainamide ethobromide (PAEB) and quinine, which were transported from plasma into liver against a concentration gradient, were greatly decreased by infusing sulfhydryl reagents, p-chloromercuribenzoic acid (PCMB), p-chloromercury phenyl sulfonic acid (PCMBS) and iodoacetamide (IAA), into portal vein on account of the increase in the plasma level and the decrease in the liver level. The metabolism of PAEB and quinine was not affected by the infusion of the reagents. The binding of APAEB, PAEB and quinine was not depressed and that to plasma was not changed in the presence of the reagents. Consequently it was deduced that the hepatic uptake of the organic cations was blocked by the treatment with the sulfhydryl reagents, which acted on the plasma membrane involved in the concentrative uptake of the organic cations. In comparison with the previous results obtained by the intrabiliary retrograde infusion, PCMB and IAA were inhibitory only on the hepatic uptake process and N-ethylmaleimide (NEM) only on the excretory process, whereas PCMBS was effective on both steps. The finding of the specific reagents which are inhibitory only on one process would be of use in the study of the hepato-biliary transport of organic cations.