Metabolism of propionyl erythromycin lauryl sulfate. I. Fate of the propionyl erythromycin moiety in the rat

Abstract

The absorption, excretion, and metabolism of propionyl erythromycin (PE) has been studied in the rat. The major routes of metabolism of PE are ester hydrolysis and N-demethylation. The rates of these two reactions have been examined in vivo using radiolabeled PE. The plasma half-life of the ester is 5.5 hr. The correlation of blood levels of radioactivity with 14CO2 production indicates that the ester is continually hydrolyzed after absorption. The half-life of the dimethyl-amino moiety of the desosamine sugar is estimated at 1.5 hr. This relatively short half-life compared to that of the ester is supported by the fact that at 3.5 hr after dosing there is twice as much desmethyl-PE in plasma as PE. After oral administration of either 14C-PE or 14C-erythromycin, 70% of the radioactivity is absorbed in 6 hr. The major route of excretion is via bile. Approximatley 40% of the absorbed dose is excreted in bile in the first 6 hr after dosing. Tissue levels of radioactivity after administration of 14C-erythromycin or 14C-PE indicate that PE or a metabolite accumulates in the tissue during chronic dosing, whereas erythromycin-related levels are similar after single or multiple doses.