Both quinidine and verapamil are known to increase the serum digoxin concentration (SDC), and other calcium channel blockers may have a similar effect. Since an increasing number of patients is likely to be treated concurrently with digoxin, quinidine and a calcium channel blocker, a study was done to show whether coadministered quinidine and verapamil would cooperate to elevate the SDC. Nine healthy volunteers on basic digoxin treatment (Leanoxin 0.125 mg t.i.d.) were treated with placebo, verapamil 80 mg t.i.d. and the combination (verapamil 80 mg plus quinidine base 160 mg t.i.d.), for 2 weeks in a randomized sequence. Drug concentration and various cardiovascular parameters were measured each week and/or at the end of each treatment period. Steady state concentrations were always obtained within 1 week and drug levels at the end of the first and second weeks of treatment were almost identical. The plasma verapamil concentration (PVC) was 25.8 +/- 9.9 ng/ml during coadministration of verapamil and digoxin, and 15.7 +/- 6.9 ng/ml during combined verapamil-quinidine coadministration, when the serum quinidine concentration (SQC) was 1.26 +/- 0.50 micrograms/ml. Compared to placebo SDC rose by 53% from 0.62 +/- 0.16 to 0.95 +/- 0.29 ng/ml (p less than 0.001) during verapamil treatment and further to 1.58 +/- 0.38 ng/ml (155% rise; p less than 0.001) during combined verapamil-quinidine coadministration. Thus each drug maintained its own effect on SDC in the presence of the other, and their actions became combined in increasing the SDC.(ABSTRACT TRUNCATED AT 250 WORDS)