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

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Abstract
3-Hydroxyquinidine [3-OH-quinidine], a major quinidine metabolite, was 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 h and blood pressure, heart rate and averaged ECG complexes were recorded during 12 h after dosing. Kinetic analysis revealed differences from published data for the parent drug. Renal clearance was 16 l/h. The elimination t1/2 [half life] was 12.4 h, substantially longer than that of quinidine. No systematic ECG changes were observed in 2 subjects with maximum concentrations of 55 and 215 .mu.g/l. In the other 2 subjects who achieved higher maximum concentrations (447 and 918 .mu.g/l), there was a significant relationship between the length of the corrected QT interval and the serum concentration of 3-OH-quinidine. 3-OH-quinidine exerts effects in man resembling those of quinidine and may contribute to the antiarrhythmic activity of quinidine.

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