Editors' ChoicePharmacology

Digoxin Dangers

Sci. Signal.  23 Jul 2013:
Vol. 6, Issue 285, pp. ec172
DOI: 10.1126/scisignal.2004529

A proportion of patients treated with digoxin, a cardiac glycoside used to treat heart function abnormalities, generate the inactive metabolite dihydrodigoxin, resulting in poor efficacy. Haiser et al. examined a potential culprit responsible for this transformation—the actinobacterium Eggerthella lenta—to probe the microbiota-digoxin interaction. Microbe growth was promoted by arginine, and differential expression analysis revealed a two-gene cardiac glycoside reductase (cgr) operon that was induced by digoxin in low-arginine conditions. Not all strains of E. lenta could reduce digoxin and, when fecal samples from healthy people were tested, a spectrum of digoxin inactivation was detected. When the digoxin-reducing strain of E. lenta was given to germ-free mice that were fed a high-protein (that is, high-arginine) diet, digoxin levels stayed high in serum, and drug inactivation was suppressed.

H. J. Haiser, D. B. Gootenberg, K. Chatman, G. Sirasani, E. P. Balskus, P. J. Turnbaugh, Predicting and manipulating cardiac drug inactivation by the human gut bacterium Eggerthella lenta. Science 341, 295–298 (2013). [Abstract] [Full Text]