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The effects of two antiarrhythmic agents, hydroquinidine and quinidine on the prevention of pacing induced sustained ventricular tachycardia (VT) were studied in 14 patients. The underlying cardiac disease was old myocardial infarction (12 patients) or dilated cardiomyopathy (2 patients). Sustained monomorphic VT was induced in 14 patients during the initial electrophysiological study performed at least 48 hours after withdrawal of all antiarrhythmic therapy. The same stimulation protocol including 3 extrastimuli (S2 S3 S4) and 2 paced cycles (600 ms and 400 ms) was repeated at least 48 hours after the administration of 600 mg (2 gelules) per 24 hours of hydroquinidine or 1100 mg of quinidine arabogalactane sulphate, 3 to 4 hours after the last dose. This was an open, randomised, crossed over trial. Irrespective of the result observed with the first antiarrhythmic, used in an order attributed by a randomised table, the other antiarrhythmic was tested. Plasma concentrations were measured during the programmed stimulation test for both drugs. Induced VT was prevented by the two antiarrhythmics in 4 patients (28%). In one patient, VT was prevented by hydroquinidine but not by the quinidine compound, resulting in a prevention rate of 35% for the hydroquinidine. On the other hand, the quinidine compound was a total success in one patient in whom only a partial success was observed with hydroquinidine. VT remained inducible with both antiarrhythmics in 9 patients (64%).(ABSTRACT TRUNCATED AT 250 WORDS)

1. The electrophysiologic effects of quinidine (Q)were studied in 15 pentobarbital-anesthetized dogs using intracardiac electrography and programmed stimulation. With four successive bolus i.v. injections of Q gluconate (1, 3, 9, 18 mg/kg cumulative doses) at 30 min intervals, Q plasma concentration (Cp) ranged from 1.02 +/- 0.1 micrograms/ml to 5.7 +/- 0.6 micrograms at the time of electrophysiologic measurements 20 min after each injection. 2. In six control dogs, heart rate (HR), sinus node recovery time (TRS), conduction times (StH, HV, QRS), ventricular repolarization time (QTc) Wenckebach cycle length (L.W), and atrial refractory periods (RP) did not change significantly while the functional nodal (PRFN) and the effective ventricular (PREV) RPs significantly increased with time. 3. Quinidine produced a significant log- Cp related decrease in HR and increase in TRS corresponding to a decreased sinus automaticity. 4. StH and HV conduction times increased proportionally to log CpQ while the increase in QRS was not Cp-dependent. QTc did not increase significantly. 5. Quinidine resulted in significant log Cp-related increases in atrial RP PRFN and LW while the Q-induced changes in PREV were not Cp-dependent.

The measurements of the plasma concentrations of antiarrhythmic drugs is useful both for studying the pharmacokinetics and bio-availability of a drug, and for assessing the relationship between pharmacological activity and plasma levels in clinical practice so that dosages may be adapted to obtain optimal efficacity in each individual patient and to avoid side-effects caused by drugs with low therapeutic indices. Many methods are available, including spectrophotometry, spectrofluorometry, gas chromatography, liquid chromatography and immuno-enzymology. The practicability, sensitivity and specificity of these techniques are compared with respect to their objectives. Particular attention is paid to the principal antiarrhythmic agents with fairly well defined zones of efficacity: procainamide, quinidine, disopyramide, propranolol, lignocaine and mexiletine.

Arabogalactane sulphate of quinidine (AGSQ) is a slow release preparation of quinidine. The aim of this study was to compare the plasma levels of quinidine obtained by different preparations of AGSQ (AGSQ I, II and III) and to determine which was best suited to therapeutics. The "in vitro" study showed different amounts of quinidine liberated in 6 hours, 34% with AGSQ I, 58% with AGSQ II and 100% with AGSQ III. The plasma quinidine levels were studied after administration of a dose corresponding to 330 mg quinidine base, morning and evening for 7 consecutive days to 27 hospitalised patients; 7 received AGSQ I, 11 received AGSQ II 5, received AGSQ III and 4 quinidine sulphate. The delay in reaching a steady state was 24 hours for the quinidine sulphate 36 hours for AGSQ I, 48 hours for AGSQ II and 60 hours for AGSQ III. The average plasma level on the 7th day (Cee) was 2.74 +/- 0.71 microgram/ml, 2.62 +/- 0.74 microgram/ml and 3.29 +/- 0.72 microgram/ml respectively. The plasma quinidine levels were maintained between toxic and therapeutic levels (3,5 and 1,7 microgram/ml) only with AGSQ II by suppressing the peak observed 1 hour administration of quinidine sulphate. An excellent correlation (r = 0,984) was observed between the plasma quinidine 6 hours after ingestion and the Cee. A blood test during the steady state, 6 hours after ingestion of the drug, is useful in adjusting the dosage. These results suggest that AGSQ II is the preparation best suited for therapeutic usage although it does not give the best relative bioavailability of the drug.