VERAPAMIL INCREASES DIGOXIN BLOOD LEVELS WHEN GIVEN CONCURRENTLY

And this enhances and prolongs digoxin's inotropic activity Eight healthy male volunteers received a single dose of digoxin (l.Omg bolus) before and after 7 days' treatment with

oral verapamil ( 120mg tid) to assess the potential interactions between the 2 drugs.

The clearance of digoxin decreased in the presence of verapamil, from 4.68 to 3.29 mlfmin/kg, and the mean

elimination half-life increased from 33.5 to 41.3 hours, but the volume of distribution of digoxin did not change

significantly. The total electromechanical systole (QS2) corrected for a heart rate of 60/min (QS2-J60) and the left

ventricular ejection time similarly corrected (LVET-160) were markedly and similarly reduced (with a maximum effect

within 7 hours) by digoxin both with and without verapamil, and paralleled changes in the mean concentrations of

digoxin, but verapamil had no significantly different effect compared with digoxin alone.

The decay of effect on LVET-160 and QSr 160 was slower in the presence of verapamil (mean half-lives of 84.9 and

74.2 hours, respectively) than with digoxin alone (40.9 and 47.8 hours, respectively), in parallel with the prolongation

of the digoxin plasma half-life. During verapamil coadministration the AUCs for QSr 160, LVET-160, and plasma

.digoxiri increased by mean values of 50, 33 and 41%, respectively. Throughout the study, BP was unaitered but heart rate showed a significant decrease within an hour of digoxin and

then gradually returned to normal. No adverse reactions were observed. Thus, verapamil coadministration with

digoxin resulted in a 30-35% reduction in the total body clearance of digoxin and in a 40% increase in the mean drug

concentration in the deep compartment. These kinetic changes were associated with a slower decay of the total inotropic effect.

Since verapamil itself does not appear to affect myocardial contractility, the enhanced inotropism seems to reflect a

verapamil-induced rise in the concentration of digoxin at the receptor level. ' It is concluded that the rise in plasma

digoxin, resulting from coadministration of verapamil to healthy subjects appeared to have been cardioactive in terms of inotropism'. Pedersen, K.E. et al.: European Journal of Clinical Pharmacology 25: 199 (No 2. 1983)

14 INPHARMA 3 Dec 1983 0156-2703/83/ 1203-0014/0$01.00/0 ° ADIS Press