Effect of erythromycin on tricyclic antidepressant metabolism

Macrolide antibiotics such as erythromycin have been found to impair the hepatic metabolism of carbamazepine. In addition, recent studies have shown that intestinal flora can N-demethylate tricyclic antidepressants, suggesting that the human gut may be a possible site of extrahepatic drug metabolism. Therefore, we conducted a study to determine whether the concurrent use of erythromycin might influence the metabolism and steady-state plasma concentrations of tricyclic antidepressants. Six days of erythromycin administration caused no systematic change in either the parent tricyclic or its metabolite(s). Thus, the short term concurrent use of erythromycin does not appear to alter hepatic or gut flora tricyclic metabolism to an appreciable extent. Nevertheless, prior reports of altered carbamazepine kinetics by erythromycin should increase the physician's awareness of a possible drug interaction when erythromycin is used concurrently with a tricyclic antidepressant.