Plasma digitoxin

Number of cases Plasma digitoxin (ng/ml) Dose blood sampling time relationship... 

Shapiro, W., Narahara, K., and Taubert, K., Relationship of plasma digitoxin and digoxin to cardiac response following intravenous digitalization in man. Circulation 42, 1065-1072 (1970). 

Verapamil and diltiazem, but not nifedipine, increase steady-state plasma digitoxin concentrations (184). 

The plasma digitoxin levels of a man were reduced on three occasions when he was given phenytoin. On the third occasion, while taking digitoxin 200 micrograms daily, the addition of phenytoin 900 mg daily caused a 60% fall in digitoxin levels (from 25 to 10 nanograms/mL) over a 7 to 10 day period. ... 

Phenytoin has a stabilising effect on the myocardial cells so that the toxic threshold of digoxin at which arrhythmias occur is raised. However, the bradycardic effects of the digitalis glycoside are not opposed and the lethal dose is unaltered, so that the cardiac arrest reported would appear to be the result of excessive bradycardia. It seems possible that the fall in plasma digitoxin levels may be due to a phenytoin-induced increase in the metabolism of the digitoxin by the liver. ... 

Five out of 10 patients taking digitoxin had a 6 to 31% (mean 21%) rise in plasma digitoxin levels while taking diltiazem 180 mg daily for 4 to 6 weeks. ... 

A study in 18 subjects showed that nifedipine 40 to 60 mg daily had no significant effect on their steady-state plasma digitoxin levels over a 6-week period. This study has also been published elsewhere. ... 

A comparative study in 11 patients with plasma digitoxin levels greater than 40 nanograms/niL found that when the digitoxin was stopped and colestipol 5 g four times daily was given before meals, the digitoxin half-life (6.3 days) was unaffected, when compared with 11 other patients not given colestipol (6.8 days). ... 

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]. 

The conclusion is inescapable that neither plasma digoxin nor digitoxin levels are infallible guides to drug-induced toxicity, but must be... 

L17. Lukas, D. S., and De Martino, A. G., Binding of digitoxin and some related cardenolides to human plasma proteins. J. Clin. Invest. 48, 1041-1053 (1969). 

Shoeman, D. W., and Azamoff, D. L., The alteration of plasma proteins in uraemia as reflected in their ability to bind digitoxin and diphenylhydantoin. Pharmacology 7, 169-177 (1972). 

The SSRIs bind tightly to plasma proteins and may interfere with other protein-bound drugs (e.g., warfarin, digitoxin), causing a shift in plasma concentrations that can potentially result in adverse effects (Schrefer, 2001). As mentioned above, the SSRI medications can... 

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. 

Kuhlmann J. Effects of verapamil, diltiazem, and nifedipine on plasma levels and renal excretion of digitoxin. Clin Pharmacol Ther 1985 38 667-673. 

CALCIUM CHANNEL BLOCKERS DIGITOXIN Plasma concentrations of digitoxin may be T by diltiazem and verapamil Uncertain at present Watch for digitoxin toxicity... 

DIGITOXIN ANTIBIOTICS - RIFAMPICIN Plasma concentrations of digitoxin may be halved by rifampicin Due to T hepatic metabolism Watch for poor response to digitoxin... 

As for digitoxin. Low plasma-potassium increases digoxin toxicity which may occur at therapeutic concentrations. 

In a fatality due to the ingestion of 15 mg of digitoxin, a plasma concentration of 0.32 pg/ml was attained 4 hours after ingestion death occurred after 14 hours (M. Mercier, Bull. int. Ass.forens. Toxicol., 1971, 7(4), 10-11). 

A subject who ingested 10 mg of digitoxin recovered following treatment with activated charcoal a plasma concentration of 0.26 ig/ml was reported 4 hours after the dose, decreasing to 0.027 gg/ml at 80 hours (S. Pond, etal.. Lancet, 1981, 2, 1177-1178). 

If the plasma digitalis concentration is below the therapeutic range (0.8 ng/ml for digoxin and 10 ng/ml for digitoxin) withdrawal is very unlikely to produce deterioration. 

Digoxin crosses the placenta and enters the neonatal circulation (130). It has therefore been used, for example, to improve fetal cardiac function (131). In normal circumstances there seem to be no adverse effects on the neonate, and neonatal plasma concentrations are below those generally considered to be therapeutic. There has been one report of fatal toxicity in the fetus of a woman who took an overdose of digitoxin (132). 

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