STUDIES ON THE METABOLISM OF ERYTHROMYCIN BASE AND ITS PROPIONYL ESTER

Abstract

Hepatic dysfunction has been frequently reported in clinical use with esters of erythromycin (EM) and oleandomycin, and these side effects have been explained with the concept of hypersensitivity by some observers.
It is said that biliary excretion of propionyl erythromycin (EMP) in human subjects is remarkably different from that of EM base, suggesting the metabolic process in these two drugs may be quite different.
This paper deals with the difference in metabolism between EM and EMP in vitro and in vivo, in regard to the cause of hepatic dysfunction due to the latter.
1) In absorption and excretion study with dogs, pro longation in half-life and marked decreases in biliary and urinary excretion have been observed following intravenous EMP dose in comparison with EM base, while blood levels of the two substances in portal vein were similar following intraduodenal dose.
2) In the study with rats and rabbits, decrease in blood level of EM was found in animals with phenobarbital pretreatment.
N-methylase activities of the rat liver were accelerated by the treatment with phenobarbital but not erythromycins. Esterase activities were unchanged in all these treatments.
3) The study of in vitro and in vivo metabolism of erythromycins with thin layer chromatography was carried out.
The results seem to indicate that EM is changed into two metabolites, i. e. des-N-methyl erythromycin and one unknown, but EMP may not be changed into EM directly, and may be passed through other metabolic process.