Plasma and tissue levels of digoxin in the rat following pretreatment with verapamil.

Verapamil and digoxin are frequently used in combination, and clinical experience suggests that verapamil may increase digoxin toxicity. We have investigated the influence of verapamil on digoxin pharmacokinetics in the rat. Rats were injected with 10 mg/kg verapamil s.c. twice a day for 7 days while control rats were injected with saline only. On the 7th day, all the rats received 0.5 mg/kg of digoxin i.p. Two, 4, 6, 8 and 10 hours later, groups of 6 to 8 verapamil pretreated and control animals were sacrificed and plasma, heart, brain, liver, kidney and muscle digoxin concentrations were assayed. Digoxin levels were significantly higher in the plasma, heart, liver and muscle of the verapamil pretreated rats at 6, 8 and 10 hours (p less than 0.01).