Chemical Structure of Erythromycin and Hepatotoxicity

The biochemical features of erythromycin estolate essential for hepatotoxicity were studied in a patient with proved erythromycin estolate toxicity. The only two variables in commercial erythromycin preparations are the chemical nature of the moiety substituted at the 2′ position and the base. By challenges with different 2′ substitutions and bases, we determined that the essential hepatotoxic property of erythromycin estolate in this patient was the propionyl ester linkage at the 2′ position and that cross-sensitivity with erythromycin estolate did not occur with plain erythromycin, erythromycin stearate, erythromycin gluceptate, or erythromycin ethylsuccinate. We were unable to directly implicate an immunologic mechanism for erythromycin estolate hepatotoxicity, since neither tissue deposits of immunoglobulins nor lymphoblastic transformation were found.