Intravenous quinidine: relations among concentration, tachyarrhythmia suppression and electrophysiologic actions with inducible sustained ventricular tachycardia.
A computer simulation was used to devise quinidine sulfate infusions to produce pseudo-steady-state concentrations in the low (8 microM/liter) and high (14 microM/liter) therapeutic ranges, avoiding high peak concentrations. Using this infusion, efficacy and electrophysiologic actions of quinidine sulfate were assessed in 21 patients with sustained inducible ventricular tachycardia (VT) when concentrations were 12.6 +/- 11 microM/liter (mean +/- standard deviation) and 18 +/- 9 microM/liter. Although mean concentrations approximated target levels, there was substantial individual variation. A reciprocal linear relation (r = 0.8, p less than 0.01) was noted between resultant serum concentrations and drug-free ejection fraction (EF). Transient hypotension occurred early in 3 patients, 2 of whom had a normal left ventricular (LV) EF. No hemodynamic compromise was seen in patients with LVEFs of less than 30%. Induced VT was suppressed in 5 patients at low concentrations and in an additional 4 at high concentrations (total 9 of 21, 42%). Concentration-dependent changes in the ventricular effective refractory period of the beat induced by S3 paralleled antiarrhythmic efficacy. Independent of response or lack of response to intravenous quinidine, 17 patients received gradually increasing oral quinidine dosages adjusted to reproduce plasma levels that had been effective during intravenous administration, or to maximal well-tolerated dosage (if side effects occurred). VT was still inducible during oral treatment in 4 of 5 patients in whom VT had been suppressed during the intravenous infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
D000284:Administration, Oral; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D007263:Infusions, Parenteral; D011802:Quinidine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D013318:Stroke Volume; D013610:Tachycardia / Q000097:blood / Q000188:drug therapy
D011802:Quinidine