Penicillin-induced changes in function of the isolated perfused rat liver: alterations in thyroxine metabolism and sulfobromophthalein excretion.

Abstract

Penicillin was found to displace thyroxine (T4) from binding sites on the plasma proteins in the isolated, perfused rat liver system. The blood levels of penicillin at the beginning of the perfusion were much higher than those attained in routine clinical use. This effect was manifested by changes in erythrocyte uptake of T4 and in the rate of disappearance of T4-13lI added to the perfusate. Penicillin induced an increase in the volume of bile produced by the perfused rat liver but markedly reduced thebiliary excretion of radioactive metabolites of T4, chiefly T4 glucuronide with smaller amounts of glucuronides of T3 and T3- Only small amounts of these glucuronides were found in blood and liver at the end of the perfusion, while large amounts of unchanged T4 and the usual amounts of radioactive iodide were present. Thus, it appeared that penicillin inhibited the conjugation of T4 and its metabolites. Penicillin also markedly reduced the biliary excretion of sulfobromophthalein (BSP). (Endocrinology 80:247...