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Applied and Environmental Microbiology Apr 1987The obligate anaerobe Eubacterium lentum inactivated the cardiac glycoside digitoxin by reducing the double bond in the lactone ring. This conversion was quantitative...
The obligate anaerobe Eubacterium lentum inactivated the cardiac glycoside digitoxin by reducing the double bond in the lactone ring. This conversion was quantitative when the substrate was incubated at a concentration of 10 micrograms/ml. The reduction reaction coincided with the growth phase of the bacterium. The stereochemical configuration at C-20 of the reduction product dihydrodigitoxin was found to be R. Incubation of digitoxigenin and its mono- and bisdigitoxosides individually with E. lentum led to the formation of their respective dihydro derivatives. The configuration at C-20 of these reduced metabolites was also found to be R.
Topics: Circular Dichroism; Digitoxin; Eubacterium; Molecular Conformation; Oxidation-Reduction
PubMed: 3579289
DOI: 10.1128/aem.53.4.901-904.1987 -
Japanese Journal of Pharmacology Jun 1968
Topics: Animals; Cardiac Glycosides; Cats; Digitoxin; Guinea Pigs; Injections, Intravenous; Myocardium
PubMed: 5303526
DOI: 10.1254/jjp.18.269 -
The Journal of Clinical Investigation Dec 1971Previous studies of digitalis glycoside metabolism and excretion have indicated that these compounds undergo a significant enterohepatic cycle in some species. It has...
Interruption of the enterohepatic circulation of digitoxin by cholestyramine. II. Effect on metabolic disposition of tritium-labeled digitoxin and cardiac systolic intervals in man.
Previous studies of digitalis glycoside metabolism and excretion have indicated that these compounds undergo a significant enterohepatic cycle in some species. It has been suggested that the existence of such a cycle in man contributes to the prolonged action of certain cardiac glycosides. Previous studies have demonstrated that cholestyramine binds digitoxin and digoxin in vitro and accelerates the metabolic disposition of digitoxin in rats and guinea pigs, presumably by interrupting the enterohepatic circulation. In order to assess the role of the enterohepatic circulation in the metabolism of digitalis glycosides in humans, maintenance doses of cholestyramine were administered to 7 of 15 normal human subjects beginning 8 hr after digitalization with 1.2 mg of digitoxin-(3)H. All subjects had frequent measurements of serum radioactivity, left ventricular ejection time (LVET), and electromechanical systole (QS(2)), the latter recorded as the interval from onset of Q wave to first major component of second heart sound. Measurement of the LVET and QS(2) intervals affords a sensitive index of the cardiac response to digitalis. In addition, chloroform extraction of serum was performed to separate unchanged digitoxin and active metabolites from cardioinactive metabolites of digitoxin. Cholestyramine treatment resulted in reduction in half-life to total serum radioactivity from 11.5 to 6.6 days, and in chloroform-extractable radioactivity from 6.0 to 4.5 days, as compared to controls. In addition, cholestyramine treatment was accompanied by more rapid return to base line values of digitoxin-induced changes in the LVET and QS(2) intervals. A significant positive correlation was found between QS(2) values and chloroform-extractable radioactivity, the latter reflecting unchanged digitoxin-H(3) (r=0.64; P=<0.01). The results indicate that administration of cholestyramine to digitalized human subjects accelerates the metabolic disposition of digitoxin and abbreviates the physiologic response to the glycoside. This effect is presumably mediated by interruption of the enterohepatic circulation of digitoxin by cholestyramine.
Topics: Administration, Oral; Adult; Carotid Arteries; Cholestyramine Resin; Chromatography, Thin Layer; Digitoxin; Electrocardiography; Heart; Humans; Liver; Male; Methods; Phonocardiography; Pulse; Time Factors; Tritium
PubMed: 5129315
DOI: 10.1172/JCI106764 -
British Journal of Clinical Pharmacology Apr 1981
Topics: Adult; Aged; Aging; Digitoxin; Female; Humans; Kinetics; Male
PubMed: 7259937
DOI: 10.1111/j.1365-2125.1981.tb01144.x -
Clinical Pharmacology and Therapeutics Mar 1986Quinidine has been reported to increase digoxin plasma concentrations, which increases the risk of digoxin overdose. The effect of quinidine on digitoxin... (Clinical Trial)
Clinical Trial
Quinidine has been reported to increase digoxin plasma concentrations, which increases the risk of digoxin overdose. The effect of quinidine on digitoxin pharmacokinetics is still controversial because most studies were not performed with subjects achieving definite steady-state conditions. To determine whether quinidine affects digitoxin kinetics and cardiac efficacy, we measured glycoside plasma concentrations and renal excretion as well as ECG parameters and systolic time intervals before and during quinidine dosing in eight healthy subjects at steady state. Mean (+/- SD) digitoxin plasma concentrations and renal excretion increased from 13.6 +/- 2.2 ng/ml and 16.1 +/- 5.8 micrograms/24 hours before dosing to 19.7 +/- 3.1 ng/ml and 23.4 +/- 4.9 micrograms/24 hours, respectively, during quinidine dosing for 32 days. While renal digitoxin clearance was not noticeably changed by quinidine, total digitoxin clearance and extrarenal digitoxin clearance decreased by an average of 32% and 40.5%, respectively. The elimination t1/2 was prolonged from 150.3 +/- 20.6 to 202.6 +/- 37.5 hours. The increased digitoxin plasma level is pharmacodynamically active. We conclude that there is a clinically important interaction between digitoxin and quinidine, but it is to a lesser extent and is caused by different mechanism, in part, than the interaction between digoxin and quinidine.
Topics: Administration, Oral; Adult; Clinical Trials as Topic; Digitoxin; Drug Interactions; Electrocardiography; Female; Glycosides; Humans; Kinetics; Male; Prospective Studies; Quinidine; Radioimmunoassay
PubMed: 3512148
DOI: 10.1038/clpt.1986.41 -
Journal of Pharmaceutical Sciences Sep 1982A rapid, selective, and simple high-performance liquid chromatographic assay for digitoxin formulations is described. The method utilizes a conventional octadecyl-bonded...
A rapid, selective, and simple high-performance liquid chromatographic assay for digitoxin formulations is described. The method utilizes a conventional octadecyl-bonded phase column with detection at 220 nm. The isocratic solvent system resolves digitoxin from its potential degradation products and provides an accurate assay for tablet and injectable formulations with a relative standard deviation of 1.4 and 3.3%, respectively. The method is sufficiently sensitive to monitor content uniformity of tablets and the minimum quantifiable amount of digitoxin was determined to be 20 ng. The total chromatograph time was approximately 15 min.
Topics: Chromatography, High Pressure Liquid; Digitoxin; Tablets
PubMed: 7131266
DOI: 10.1002/jps.2600710916 -
Chemical & Pharmaceutical Bulletin May 1970
Topics: Culture Techniques; Digitalis; Digitoxin; Plants, Medicinal; Plants, Toxic
PubMed: 5419241
DOI: 10.1248/cpb.18.1080 -
European Journal of Clinical... 1985Eight healthy volunteers were studied to ascertain the effect of digoxin and the relatively more lipophylic cardiac glycoside, acetyl-digitoxin on ventilation. Baseline...
Eight healthy volunteers were studied to ascertain the effect of digoxin and the relatively more lipophylic cardiac glycoside, acetyl-digitoxin on ventilation. Baseline ventilation as well as the response to the inspiration of 2.2% and 4.8% carbon dioxide were assessed. Digoxin produced a depression of minute volume and oxygen consumption whereas acetyl-digitoxin produced the opposite effect. This could be the result of a relatively greater vagomimetic effect with digoxin and a greater symphatomimetic effect with acetyl-digitoxin. These findings might have clinical implications in cardiac patients who have pulmonary disease.
Topics: Acetyldigitoxins; Adult; Carbon Dioxide; Digitoxin; Digoxin; Female; Humans; Male; Oxygen Consumption; Respiration; Systole
PubMed: 3921385
DOI: 10.1007/BF00609684 -
Wiener Klinische Wochenschrift Dec 1984In most cases pacemaker patients represent a diverse geriatric group in which ECG and clinical signs are of minor usefulness in diagnosing digitalis toxicity. We...
In most cases pacemaker patients represent a diverse geriatric group in which ECG and clinical signs are of minor usefulness in diagnosing digitalis toxicity. We therefore determined serum glycoside concentrations in 200 consecutive patients attending our pacemaker clinic (with a mean maintenance dose of 0.093 mg digitoxin per day) and tried to correlate these to clinical, ECG and chemical findings. Multivariate analyses were also carried out to assess whether serum digitoxin concentrations lay in a subtherapeutic (0 to 8.99 ng/ml), therapeutic (9 to 27 ng/ml) or toxic (above 27 ng/ml) range on the basis of a combination of variables. The mean digitoxin concentration was 24.0 +/- 10.3 ng/ml (0 to 45 ng/ml) and correlated poorly with patient compliance (r = 0.36), serum potassium (r = 0.24), weight (r = 0.17) and digitoxin dose (r = 0.13), but not with ECG and subjective or clinical findings. A prediction of the three ranges of the serum digitoxin concentration was possible by means of variable compliance, body weight and digitoxin dose with a probability of up to 79%. In view of the above-mentioned problems indications for digitalis therapy in pacemaker patients must be constantly reviewed and control determination of serum digitoxin concentration should be frequently undertaken.
Topics: Adult; Aged; Cardiac Complexes, Premature; Digitoxin; Electrocardiography; Female; Humans; Male; Middle Aged; Pacemaker, Artificial; Patient Compliance; Tachycardia
PubMed: 6084909
DOI: No ID Found -
European Journal of Clinical... 1992The chronic oral administration of 0.07 mg digitoxin o.d. for up to 58 days to 12 healthy volunteers caused a small drop in mean heart rate HR (95% CI: -7.9 to -1.6... (Clinical Trial)
Clinical Trial Comparative Study
The chronic oral administration of 0.07 mg digitoxin o.d. for up to 58 days to 12 healthy volunteers caused a small drop in mean heart rate HR (95% CI: -7.9 to -1.6 beats.min-1), in mean diastolic blood pressure (95% CI: -8.3 to -0.4 mmHg), shortening of the QTc-interval (95% CI: -42 to -19 ms), shortening of the HR-corrected pre-ejection period PEPc (95% CI: -16 to -1 ms) and electromechanical systole QS2c (95% CI: -25 to -1 ms), and an increase in the impedance cardiographic Heather index (dZ/dtmax/RZ, 95% CI: 0.3 to 4.3) relative to the baseline measurements before digitalisation. The concomitant administration of 25 mg oral captopril b.d. did not significantly alter these responses relative to the concomitant double-blind administration of placebo, nor did it alter the pharmacokinetic characteristics of plasma digitoxin at steady state. Thus, no relevant change in the pharmacokinetic and pharmacodynamic characteristics of chronically administered digitoxin were induced by concomitant treatment with captopril.
Topics: Administration, Oral; Adult; Blood Pressure; Captopril; Digitoxin; Drug Interactions; Female; Heart Rate; Humans; Male
PubMed: 1451730
DOI: 10.1007/BF02220626