Verapamil and digoxin: interactions in the rat.

Verapamil and digoxin are often used in combination and clinical experience suggests that verapamil may increase digoxin toxicity. We have explored the effects of verapamil upon digoxin induced tachyarrhythmias and have undertaken a preliminary study of the influence of verapamil on digoxin pharmacokinetics in the rat. Anesthetized rats received 20 mg/kg of digoxin intraperitoneally followed by verapamil i.v., 0.3 mg/kg, in repeated doses either immediately after digoxin or only after the onset of digoxin induced arrhythmias. Digoxin alone produced prolonged paroxysmal atrial tachycardia in 88-100% of rats and verapamil converted 75% of rats to sinus rhythm and significantly reduced digoxin induced mortality. In a later study, rats were injected with 10 mg/kg verapamil i.p. twice a day for 7 days or only with saline. On the seventh day all the rats received 0.5 mg/kg of digoxin i.p. Eight hours later the animals were sacrificed and plasma, heart, brain, liver, kidney and muscle (diaphragm) digoxin concentration was measured by radioimmunoassay. Digoxin levels were twice as high in plasma, heart, liver and muscle of verapamil pretreated rats (p less than 0.01). Two types of verapamil - digoxin interactions are demonstrated in the above studies; one in which verapamil modifies digoxin induced arrhythmias and a second pharmacokinetic effect in which pretreatment with verapamil increases digoxin concentration in the plasma and in several tissues.