Inactivation of digoxin by the gut flora: reversal by antibiotic therapy.

In approximately 10 per cent of patients given digoxin, substantial conversion of the drug to cardioinactive, reduced metabolites (digoxin reduction products, or DRPs) occurs. The site and clinical importance of this conversion is unknown. In four normal volunteers taking digoxin daily for four weeks, urinary excretion of DRPs was greatest after a poorly absorbed tablet was ingested, and least after intravenous administration, Stool cultures from subjects known to make DRPs in vivo ("excretors") converted digoxin to DRPs; cultures from nonexcretors did not. Three excretors were given tablets for 22 to 29 days. A five-day course of erythromycin or tetracycline, administered after a base-line period of 10 to 17 days, markedly reduced or eliminated DRP excretion in urine and stool. Serum digoxin concentrations rose as much as twofold after antibiotics were given. We conclude that in some persons digoxin is inactivated by gastrointestinal bacteria. Changes in the enteric flora may markedly alter the state of digitalization.

[1]  V. P. Butler,et al.  Urinary excretion of reduced metabolites of digoxin. , 1981, The American journal of medicine.

[2]  S. M. Kalman,et al.  Digoxin metabolism in patients. , 1978, Archives of Internal Medicine.

[3]  M. Ahmed,et al.  Fractionation of tritiated digoxin and dihydrodigoxin with DEAE-sephadex LH-20. , 1976, Journal of chromatography.

[4]  J. Caldwell,et al.  Biliary excretion of digoxin in man , 1976, Clinical pharmacology and therapeutics.

[5]  J. Landon,et al.  The measurement of urinary digoxin and dihydrodigoxin by radioimmunoassay and by mass spectroscopy. , 1975, Clinica chimica acta; international journal of clinical chemistry.

[6]  V. P. Butler,et al.  Serum digitalis measurements in the assessment of digitalis resistance and sensitivity. , 1975, The American journal of medicine.

[7]  Marcus Fi,et al.  The reactivity of derivatives of digoxin and digitoxin as measured by the Na-K-atpase displacement assay and by radioimmunoassay. , 1975 .

[8]  J. Preibisz,et al.  Digoxin tablet bioavailability: single-dose and steady-state assessment. , 1974, Annals of internal medicine.

[9]  M. N. Margolies,et al.  Renal and gastrointestinal excretion of ouabain in dog and man. , 1974, The Journal of pharmacology and experimental therapeutics.

[10]  R R Scheline,et al.  Metabolism of foreign compounds by gastrointestinal microorganisms. , 1973, Pharmacological reviews.

[11]  V P Butler,et al.  Correlation of digoxin-tablet dissolution-rate with biological availability. , 1973, Lancet.

[12]  S. M. Kalman,et al.  The surface interaction between digoxin and cultured heart cells. , 1972, The Journal of pharmacology and experimental therapeutics.

[13]  K. Hellström,et al.  The absorption of orally administered (12 - 3 H)digoxin in man. , 1972, Clinical science.

[14]  J. Doherty,et al.  Tritiated Digoxin: XIV. Enterohepatic Circulation, Absorption, and Excretion Studies in Human Volunteers , 1970, Circulation.

[15]  E. Haber,et al.  Determination of therapeutic and toxic serum digoxin concentrations by radioimmunoassay. , 1969, The New England journal of medicine.

[16]  R. Luchi,et al.  Unusually large digitalis requirements. A study of altered digoxin metabolism. , 1968, The American journal of medicine.

[17]  G. W. Snedecor.  STATISTICAL METHODS , 1967 .

[18]  R. Vick,et al.  Effects of dihydro-ouabain, dihydrodigoxin and dihydrodigitoxin on the heart-lung preparation of the dog. , 1957, The Journal of pharmacology and experimental therapeutics.

[19]  I. Bekersky,et al.  Influence of gut microflora on bioavailability. , 1979, Drug metabolism reviews.

[20]  P. Goldman.  Biochemical pharmacology of the intestinal flora. , 1978, Annual review of pharmacology and toxicology.

[21]  E. Erdmann,et al.  Ouabain-receptor interactions in (Na+ plus K+)-ATPase preparations. IV. The molecular structure of different cardioactive steroids and other substances and their affinity to the glycoside receptor. , 1974, Naunyn-Schmiedeberg's archives of pharmacology.