Absorption of digitoxin

Digitalis glycosides [NE] Decreased gastrointestinal absorption of digitoxin (possibly also digoxin). 

In rats etacrynic acid inhibited the absorption of digitoxin from the small intestine (37), but an interaction of this sort has not been described in man. 

Oral absorption of digitoxin is rapid and complete. It is extensively metabolized in the liver to several active metabolites including digoxin. Protein binding is 97%. The volume of distribution approximates... 

Because digitoxin is a nonpolar, lipophilic glycoside, absorption from the GI tract is complete. About 90% of the dmg in plasma is tightly bound to protein. It is metabolized in the Hver to many metaboHtes, including digoxin which is the only pharmacologically active metaboHte. The dmg is excreted via the bile into feces. The elimination half-life of digitoxin is seven to nine days (87). 

Intestinal absorption of digoxin is less complete compared to digitoxin. In order to improve absorption, acetylated- and methylated-digoxin derivates were developed. Digitoxin is metabolised in hepatic microsomal enzymes and can be cleared independently from renal function. The therapeutical serum level of digoxin is 0.5-2.0 ng/ml and 10-35 ng/ml of digitoxin. Steady state plateau of therapeutic plasma concentrations is reached after 4-5 half-life-times using standard daily doses [5]. 

At the required dosage, the resins cause diverse gastrointestinal disturbances. In addition, they interfere with the absorption of fats and fat-soluble vitamins (A, D, E, K). They also adsorb and decrease the absorption of such drugs as digitoxin, vitamin K antagonists, and diuretics. Their gritty texture and bulk make ingestion an unpleasant experience. 

The principal precaution with use of the bile acid resins is the possibility of impaired absorption of other drugs given orally at the same time. Cholestyramine and colestipol can bind many other drugs, such as digitoxin, phenobarbital, chlorothiazide, and warfarin, and delay or prevent their absorption. For this reason, other drugs should always be taken at least 1 hour before or 4 to 6 hours after the resin. The resins can also decease absorption of fat-soluble vitamins. 

Among the cardiac glycosides, digitoxin is absorbed rapidly and completely from the gastrointestinal tract with oral absorption of approximately 90 to 100 percent with plasma protein binding of approx. 95 percent with plasma half life of 5 to 7 days. It enters the liver cells where it is metabolised to epidigitoxigenin and is excreted in bile and urine. 

Certain combinations of cjdotoxic drugs (cyclophosphamide, vincristine, and prednisone, with and without procarbazine) reduced plasma digoxin concentrations by about 50% during treatment with beta-acetyldigoxin, perhaps through impaired absorption of beta-acetyldigoxin (202) digitoxin was not affected (203). 

Braun W, Damm KH. Drug interactions in intestinal absorption of H-digitoxin in rats. Experientia 1976 32(5) 613-14. 

Digoxin, digitoxin + colestyramine Greatly reduced absorption of digitalis alkaloids with concurrent administration Binding effect (anionic resin) Space doses by about 8 h... 

Colestipol appears not to interfere with the absorption of either digoxin or digitoxin if it is given at least 1.5 hours after the digitalis glycoside. 

Quinidine reduces the renal excretion of digoxin by 40 to 50%, and it also appears to have some effects on non-renal clearance, which includes a reduction in digoxin excretion in the bile. There is also evidence that increases in the rate and extent of absorption of digoxin from the gut occur. More recent studies show that the mechanism behind these effects on absorption and renal excretion is likely to be P-glycoprotein inhibition by quinidine.Digoxin also appears to cause a small reduction in the renal clearance of quinidine. Quinidine appears to increase digitoxin serum levels by reducing its non-renal clearance. 

B14. Bjorn, B., Hellstrom, K., and Rosen, A., Fate of orally administered H digitoxin in man with special reference to the absorption. Circulation 43, 852-861 (1971). 

Digoxin susceptible to alteration of gastrointestinal absorption. Digitalis toxicity may be increased by drug-induced electrolyte imbalance (eg, hypokalemia). Digitoxin metabolism inducible. Renal and nonrenal excretion of digoxin susceptible to inhibition. 

Cardenolides vary in their absorption, distribution, metabolism, and excretion, as shown by comparison of three representative agents digoxin, digitoxin, and ouabain (Table 13-2). Of these three, digoxin is the only preparation used in the USA. 

Spectrofluorimetry differs from absorption spectrophotometry in not yielding an absolute scale of values. For this reason it is essential to employ a reference standard for quantitative measurements. For example, some pharmacopoeial tests, such as the test for uniformity of content for digitoxin tablets, employ a spectrofluorimefric assay and comparison wi an ofticial reference standard. Quantitative Spectrofluorimetry has been proposed for a munber of naturally fluorescent compoimds, including ergometrine, riboflavine, tiie catechol-amines, phenothiazines, the barbiturates (at pH 13), and certain antibiotics such as chlortetracycline and oxytetracycline. 

ReisseU P, Manninen V. Effect of administration of activated charcoal and fibre on absorption, excretion and steady state blood levels of digoxin and digitoxin. Evidence for intestinal secretion of the glycosides. Acta Med Scand Suppl 1982 668 88-90. 

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