Erythromycin metabolism

Anandatheerthavarada, H.K. etal. (1999) Physiological role of the N-terminal processed P4501A1 targeted to mitochondria in erythromycin metabolism and reversal of erythromycin-mediated inhibition of mitochondrial protein synthesis./oumoi of Biological Chemistry, 274 (10), 6617-6625. 

Craig PI, Tapner M, Farrell GC. Interferon suppresses erythromycin metabolism in rats and human subjects. Hepatology 1993 17 230-235. 

Maintenance doses widely vary among patients (e.g., from 1 to 20 mg/day for warfarin), and are influenced by diet (variable vitamin K intake) and medications that affect coumarin metabolism (decreased drug clearance e.g., cotrimoxazole, amiodarone, erythromycin increased clearance e.g., barbiturates, carbamaze-pine, rifampin). Thus, regular monitoring is needed... 

Theoretically buprenorphine metabolism could be inhibited by itraconazole, ketoconazole, grapefruit juice, and erythromycin or any other CYP3A4 inhibitor the effects may be greater than expected for the dose of buprenorphine being given may need to decrease buprenorphine dose. 

Drug interactions Metabolized by CYP450 3A4 (e.g., cyclosporine, erythromycin, itraconazole, phenytoin, St. John s wort)... 

Stassi, D.L., Kakavas, S.J., Reynolds, K.A. cl al. (1998) Ethyl-substituted erythromycin derivatives produced by directed metabolic engineering. Proceedings of the National Academy of Sciences of the United States of America, 95, 7305. 

Reeves, A.R., Cemota, W.H., Britain, I.A. et al. (2004) Engineering precursor flow for increased erythromycin production in Aeromicrobium erythreum. Metabolic Engineering, 6, 300-312. 

This has been confirmed in activity studies where the rates of metabolism of midazolam [19] and erythromycin [14] have been studied in microsomes from... 

Tab. 13.4. Metabolism of midazolam and erythromycin in microsomes from human duodenum, jejunum and ileum.

Ketoconazole (a potent inhibitor of CYP3A4) has been shown to increase the oral bioavailability of cyclosporin from 22 to 56% [50]. This consisted of a 1.8-fold decrease in systemic clearance combined with a 4.9-fold decrease in oral clearance. The authors estimated that hepatic extraction was decreased only 1.15-fold, whereas the oral bioavailability increased 2.6-fold and the observation was attributed to decreased intestinal metabolism. Erythromycin was also shown to increase the oral bioavailability of cyclosporin A 1.7-fold, while pre-treatment with rifampin (an inducer of CYP3A4) decreased oral bioavailability of cyclosporin from 27% to 10% due to a 4.2-fold increase in oral clearance but only a 1.2-fold increase in systemic clearance. Floren et al. [51] have also shown that ketoconazole can double the oral bioavailability of tacrolimus in man by inhibiting gut wall CYP3A4. 

Carbamazepine may interact with other drugs by inducing their metabolism. Valproic acid increases concentrations ofthe 10,11-epoxide metabolite without affecting the concentration of carbamazepine. The interaction of erythromycin and clarithromycin (CYP3A4 inhibition) with carbamazepine is particularly significant. 

Interactions Antacids ciclosporin colestipol druas metabolized bv cytochrome P450 3A4 fibrates oral-contraceptiyes warfarin niacin erythromycin diaoxin azole-antifunaals... 

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