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The effects of aprindine hydrochloride, an antiarrhythmic drug of the class IB, on heart rate variability were evaluated in 13 patients (eight men and five women), ages 76 ± 11 years, who showed a standard deviation of the R-R interval measured at 5-minute intervals (SDANN) of ⩽100 msec on 24-hour electrocardiograms. After 24-hour electrocardiograms were recorded during the control period, aprindine was administered at a dose of 60 mg/day. After 2 weeks of treatment 24-hour electrocardiograms were again recorded. The SDANN was ⩽100 msec (mean, 69.3 ± 17.0 msec) in all patients during the control period, but increased after aprindine administration (mean, 86.1 ± 31.5 msec, P

Aprindine hydrochloride was administered orally to 10 patients with ventricular premature contractions in dosages of 10mg and/or 20mg at intervals of 8 hours. Plasma concentration was analyzed to clarify the process of reaching the steady state and the subsequent elimination state. The plasma concentration reached steady statewithin one to two weeks. There were very little diurnal and day-to-day variations in the plasma concentration, so a stable therapeutic level was maintained. Increased dosages from 30 to 60 mg per day resulted in threefold plasma concentration increase from 0.28 to 0.89μg/ml in steady state. The decline of aprindine hydrochloride after the last dose deviated from first-order kinetics, showing a convex decreasing curve on semilogarithmic graph paper.These results demonstrate nonlinear pharmacokinetics for aprindine hydroch loride.

An investigation of the products resulting from the photolysis of aprindine hydrochloride is described. The compounds were characterized by GLC spiking experiments and combined GLC-mass spectrometry. In some cases, R f values derived from TLC and/or preparative TLC and subsequent high-resolution mass spectral measurements also were employed for identification.

• Aprindine hydrochloride is an antiarrhythmic agent presently undergoing clinical trials in the United States. Because of the narrow therapeutic-toxic ratio observed for aprindine, the long-term follow-up of these patients is important in determining the potential clinical effectiveness of this drug. In this report we examine our experience with 30 patients with drug-resistant arrhythmias who were discharged receiving aprindine and who were followed up for a mean period of 25 months. (Arch Intern Med1983;143:2131-2133)

Aprindine hydrochloride is an antiarrhythmic drug now under investigation. The drug is most effective in prophylaxis of ventricular dysrhythmias. Previously recognized toxic effects include neurological side effects, nausea, vomiting, as well as a reported association with agranulocytosis. To our knowledge, this is the first report of agranulocytosis associated with documented elevated serum concentrations of aprindine. Further correlation of drug levels with toxic reactions may help in establishing the mechanism of bone marrow suppression. (Arch Intern Med139:1181-1182, 1979)

• Aprindine hydrochloride has been extensively used in Europe for the management of ventricular and supraventricular arrhythmias. Success has been achieved even in those cases that have proven refractory to standard antiarrhythmic agents. In this report, we describe our experience with aprindine therapy in seven patients with ventricular tachycardia in whom standard antiarrhythmic agents had proven either ineffective or had caused intolerable side effects. Aprindine was effective in five cases, and it failed in two. Neurologic side effects, although common, were easily controlled with adjustment of the dose. Agranulocytosis, a rare but serious side effect, was encountered in one of our patients. Relevant literature on aprindine is reviewed. ( Arch Intern Med 1983;143:229-232)