Quinidine-digoxin interaction: cardiac efficacy of elevated serum digoxin concentration

Cardioactivity due to elevated serum digoxin concentration (SDC) after quinidine (Q) and digoxin (D) was evaluated in six healthy subjects by means of measurement of systolic time intervals (STIs). Each subject randomly received basic treatments with 0.2 mg D and placebo (PL1). Randomized coadministrations with Q (1 gm/day), sparteine (SP) (0.8 gm/day), and placebo (PL2) were given for 7-day periods. A steady-state dose of 0.4 mg D was added. Mean SDC increased from 0.48 ng/ml during 0.2 mg D + PL2 to 1.13 ng/ml on 0.2 mg D + Q (P less than 0.05); it was unchanged by SP. On 0.4 mg D there were further shortenings of STIs compared to those on 0.2 mg D + PL2. Q markedly prolonged STIs; the SP effects were similar but less pronounced. When given with Q or SP, the effect of D was obscured by opposing inotropic properties; consequently, despite increasing SDC, measureable STIs were unchanged. The true glycoside effect was determined by comparing the effects of the pure antiarrhythmic to those of the antiarrhythmic with D. These calculations showed that the glycoside effect of the elevated SDC during Q + D dosing was much the same as the effect of 0.4 mg D.