Pharmacodynamics of a single dose of quinidine during chronic digoxin treatment

Summary

The influence of single doses of quinidine sulphate (Q) 0.5 g, sparteine sulphate (SP) 0.2 g, and placebo (PL) on heart rate-corrected systolic time intervals (STI) (QS₂c, PEPc, LVETc) and on QTc duration was studied 2 and 4 h after treatment of six healthy volunteers. All measurements were done twice in a double blind fashion, once under digoxin (D) steady state (β-methyl digoxin 0.3 mg daily) and once after an equally prolonged basic treatment period with PL. All basic treatment periods and single dose periods were randomized. Drug effects were estimated by comparison with the results obtained after administration of the corresponding placebo. The data were analyzed by two-factorial multivariate analysis of variance. Steady state digoxin serum concentrations averaged 1.3 µg/l and there was no significant change following antiarrhythmic drugs compared to PL. Single oral doses of Q and SP resulted in mean serum concentrations of about 1.8 mg/l and 0.25 mg/l, respectively. In non-digitalized subjects Q 0.5 g resulted in a lengthening of QS₂c (+15 ms), LVETc (+13 ms) and QTc (+65 ms). With SP 0.2 g similar but smaller effects were seen. D alone resulted in shortening of QS₂c (−21 ms), LVETc (−14 ms), and QTc (−32 ms). Pretreatment with D did not influence the effects of Q on the various parameters. However, corresponding to the D-induced changes in STI, a parallel shift of the curve was observed. The effects of sparteine were somewhat reduced by D. Most of the effects of Q compared to PL and SP were statistically significant (p<0.05) during both basic treatments, and the D basic treatment had a statistically significant effect for all treatment regimens, but there was no significant interaction between them. In contrast to others, the present results indicate that the positive inotropic effect of D persists in the presence of Q and SP, and that the antiarrhythmic drugs induce negative inotropic effects independent of basic treatment with D. Under the conditions of this experiment, each drug maintains its negative or positive effect on inotropy, thus resulting in an almost arithmetical superposition of the separate drug effects.