Pharmacodynamic and pharmacokinetic aspects pertinent to the potential clinical application of unbound quinidine levels were studied. Following heparin administration during electrophysiologic testing in 10 patients receiving quinidine, there were significant increases in the mean (± SD) right ventricular effective refractory period (266 ± 24 versus 279 ± 23; p < 0.025), free fatty acid concentration (515 ± 213 versus 1071 ± 359 mmol/L; p < 0.001), and unbound quinidine concentration (0.3 ± 0.1 to 0.6 ± 0.1 μg/ml; p < 0.001) but no changes in heart rate, corrected QT interval, or total plasma quinidine concentration. Ten control patients showed no change in the right ventricular effective refractory period following heparin administration. These findings were consistent with a heparin-induced increase in unbound drug concentration and activity that was limited to the vascular compartment. Eleven patients studied on day 3 (±1) and day 10 (±3) during an acute myocardial infarction showed a significant decrease in unbound quinidine fraction (12 ± 4% versus 9 ± 4%; p < 0.02) accompanied by a decrease, rather than the predicted increase, in half-life (7.1 ± 2.7 versus 6.3 ± 2.1 hours; p < 0.02). Volumes of distribution remained stable while the mean quinidine clearance tended to increase. Half-life correlated with albumin changes (r = -0.71; p < 0.02). Apparently, improvement in clinical status (assumed) and drug clearance (measured) negated the direct effects of the decrease in unbound quinidine fraction. Although unbound drug concentrations should correlate best with drug dynamic and kinetic information, full knowledge of the clinical context of such measurements is needed for appropriate interpretation.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine