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Prevalence of high (3s)‐3‐hydroxyquinidine/quinidine ratios in serum, and clearance of quinidine in cardiac patients with age
Author(s) -
Drayer Dennis E,
Hughes Miranda,
Lorenzo Beverly,
Reidenberg Marcus M
Publication year - 1980
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.1980.11
Subject(s) - quinidine , metabolite , chemistry , pharmacology , active metabolite , free fraction , distribution (mathematics) , pharmacokinetics , medicine , biochemistry , mathematical analysis , mathematics
In the sera from 42 patients receiving quinidine, (3S)‐3‐hydroxyquinidine (3‐OH), an active metabolite of quinidine, and quinidine were determined by high‐pressure liquid chromatography with fluorescence detection. These results were added to those of 25 other patients reported previously. 4 The 3‐OH/quinidine ratio averaged 0.34 ± 0.17 (SD) with a range of 0.10 to 0.90. Eleven patients (16%) had ratios above 0.50. After adjusting for protein binding differences between the 2 compounds, these 16% had 3‐OH concentrations in serum water greater than that of quinidine. An additional 7 patients (10% of the total) had levels of this metabolite in serum water slightly less than that of quinidine. A histogram showing the frequency distribution of 3‐OH/quinidine in serum indicates extensive skewing with possibly a bimodal distribution with the antimode at 0.50. Thus, 3‐OH may make a significant contribution to the effect of quinidine therapy in a fraction of treated patients. The clearance of quinidine decreased with age, indicating the need for, on the average, higher doses of quinidine in the young. Clinical Pharmacology and Therapeutics (1980) 27, 72–75; doi: 10.1038/clpt.1980.11