Prevalence of high (3S)-3-hydroxyquinidine/quinidine ratios in serum, and clearance of quinidine in cardiac patients with age

Abstract

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. 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.