Kinetics and dynamics of quinidine-N-oxide in healthy subjects.
The pharmacokinetics of a major metabolite of quinidine in humans, quinidine-N-oxide, were investigated after single oral doses (3 to 15 mg) in four healthy subjects. The concentration in serum and urine was determined by an HPLC assay. Because of a small volume of distribution, the elimination half-life of quinidine-N-oxide was only 2.5 +/- 0.28 hours (mean +/- SD), considerably shorter than that of quinidine. The renal clearance was 1.3 +/- 0.3 L/hr. Only 13.9% +/- 3.7% of the dose was recovered in urine as unchanged compound for up to 12 hours. Two unidentified compounds with the same retention time as quinidine and 3-hydroxyquinidine were found in the urine samples of two subjects. The free fraction in serum was 3.3% +/- 0.83%. No systematic changes in heart rate-corrected QT interval were observed up to concentrations of 500 ng/ml. The results indicate that quinidine-N-oxide, in contrast to 3-hydroxyquinidine, does not possess quinidine-like pharmacologic activity.
D000284:Administration, Oral; D000328:Adult; D003497:Cyclic N-Oxides / Q000008:administration & dosage / Q000097:blood* / Q000652:urine; D006801:Humans; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D011802:Quinidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000652:urine
D003497:Cyclic N-Oxides; C045112:quinidine-N-oxide; D011802:Quinidine