Add time:08/01/2019         Source:sciencedirect.com

Recent reports indicate that the metabollte of quinidine, 3-hydroxyquinidine, is pharmacologically active. It was the primary purpose of this study to determine total and unbound concentrations of quinidine and 3-hydroxyquinidine in 25 patients receiving quinidine for therapoutic purposes. At the peak, total quinidine and 3-hydroxyquinidine concentrations were 2.7 ± 1.2 μg/ml and 0.57 ± 0.33 μg/ml, respectively, and at the trough they averaged 2.0 ± 0.91 μg/ml and 0.44 ± 0.25 μg/ml. Interestingly, the unbound 3-hydroxyquinidine concentration frequently exceeded the unbound quinidine concentration, averaging 0.30 ± 0.28 μg/ml at the peak and 0.22 ± 0.14 μg/ml at the trough. Quinidine concentrations averaged 0.24 ± 0.15 μg/ml and 0.18 ± 0.12 μg/ml. The ratio of unbound 3-hydroxyquinidine: quinidine was significantly influenced by the unbound clearance of quinidine (r = 0.65). At low clearance values concentrations of both substances were elevated, with the quinidine concentration consistently exceeding that of 3-hydroxyquinidine. In contrast, at high clearance values 3-hydroxyquinidine concentrations were elevated and consistently exceeded the quinidine concentration. Thus, when quinidine concentrations are used to monitor the pharmacodynamic effect of quinidine, it is most appropriate to evaluate unbound concentrations of both quinidine and 3-hydroxyquinidine.

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