Experimental bases for the different hepatotoxicity of erythromycin preparations in man.

Abstract

Abstract Erythromycin estolate is more cytotoxic than erythromycin base or stearate on Chang cell cultures, as measured by viability and by leakage of lactate dehydrogenase and β-glucuronidase in tissue culture media. This difference correlates with their known hepatotoxic potential in patients. Erythromycin estolate is made by the combination of sodium lauryl sulfate and erythromycin propionate. We compared the in vitro cytotoxicity of these compounds independently and in combination at different concentrations. Erythromycin estolate and propionate are the only derivatives with cytotoxic potential and certain doses of sodium lauryl sulfate added to erythromycin propionate have a potentiating cytotoxic effect. Erythromycin estolate has the greatest surfactant activity of all the other derivatives tested, in vitro. Oral administration of erythromycin estolate or 14 C-labeled sodium lauryl sulfate to human volunteers and rats resulted in considerable absorption and bile excretion of the latter, hitherto assumed to be a nonabsorbable drug. The greater hepatotoxic potential or erythromycin estolate in man might be related to single or synergistic effect of its components depending on the concentrations achieved in the liver of hypersensitive patients.