Kinetics and electrocardiographic changes after oral 3-OH-quinidine in healthy subjects

Abstract

3-OH-quinidine, a major quinidine metabolite, has been reported to have antiarrhythmic activity in animals and is suspected to contribute to the effect of quinidine in man. Four healthy subjects received 3-OH-quinidine in increasing oral doses (35, 100, 300 mg) to achieve serum concentrations in the range of those after quinidine dosing in patients. Blood and urine were collected up to 48 hours and blood pressure, heart rate, and averaged ECG complexes were recorded during 12 hours after dosing. Kinetic analysis revealed differences from published data for the parent drug. Renal clearance was 16 L/hr. The elimination t1/2 was 12.4 hours, substantially longer than that of quinidine. No systematic ECG changes were observed in two subjects with maximum concentrations of 55 and 215 micrograms/L. In the other two subjects who achieved higher maximum concentrations (447 and 918 micrograms/L), there was a significant relationship between the length of the corrected QT interval and the serum concentration of 3-OH-quinidine. These first dynamic results indicate that 3-OH-quinidine exerts effects in man resembling those of quinidine and may contribute to the antiarrhythmic activity of quinidine.