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Kinetics and dynamics of quinidine‐ N ‐oxide in healthy subjects
Author(s) -
Ha HuyRiem,
Vozeh Samuel,
Uematsu Toshihiko,
Guentert Theodor W,
Follath Ferenc
Publication year - 1987
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1987.158
Subject(s) - quinidine , urine , metabolite , pharmacokinetics , chemistry , volume of distribution , pharmacology , medicine , biochemistry
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. Clinical Pharmacology and Therapeutics (1987) 42, 341–345; doi: 10.1038/clpt.1987.158