The Effect of Phenytoin on the Tissue Concentrations of Digoxin in the Rat

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Abstract
Rats treated chronically with digoxin were treated with 2 different dose levels of phenytoin, either as a single dose or chronically. Digoxin concentrations were measured by radioimmunoassay in the serum, urine, heart, muscle, liver and kidney. Chronic treatment with the high phenytoin dose significantly increased digoxin levels in serum and tissues and decreased renal clearance of digoxin. The low phenytoin dose significantly reduced serum and tissue levels of digoxin and increased renal clearance. Single phenytoin doses had a tendency to cause similar changes. Digoxin levels were altered during phenytoin treatment. In contrast to man, digoxin is extensively metabolized in the rat. Enzyme induction in connection with low phenytoin dosage and inhibition by high dosage is the suggested mechanism. The tissue distribution and excretion of digoxin are probably altered. The antiarrhythmic properties of phenytoin are generally known. It has been shown to be especially effective in treatment of digitalis toxicity induced arrhythmias.