Active transport of quaternary ammonium compounds into bile

¹ Laboratory of Chemical Pharmacology, National Heart Institute, National Institutes of Health, Bethesda, Maryland

The quaternary ammonium ion, procaine amide ethobromide (PAEB), administered intravenously (5 mg/kg) to rats with ligated renal pedicles, rapidly appears in the bile in high concentrations, both as free PAEB and as conjugated PAEB. During 1 hr after administration of the compound, the biliary concentrations of free as well as conjugated compound are about 80 times greater than the plasma concentrations. Raising the dose of PAEB does not result in an increased excretion of the compound, indicating that the excretion process is saturable. A number of quaternary amine compounds markedly depress the excretion of PAEB while others do not, suggesting a competition for transport and a certain degree of specificity for the transport process. The results indicate that the liver has an active secretory process for the transport of certain quaternary ammonium ions from blood to bile. The process appears to be different from that which actively secretes organic anions such as Bromsulphalein, bile acids, and fluorescein, since high doses of Bromsulphalein and sodium glycocholate do not inhibit the transport of PAEB.