Guentert T W, Upton R A, Holford N H, Riegelman S
J Pharmacokinet Biopharm. 1979 Jun;7(3):303-11. doi: 10.1007/BF01060020.
Previously published estimates of pharmacokinetic characteristics of quinidine can be shown to be dependent on whether the investigators have used analytical methods which are specific for quinidine. Areas under the plasma concentration-time curve and peak plasma concentrations after administration of the drug were higher and clearance values consequently lower in studies utilizing nonspecific assays unable to distinguish quinidine from its metabolities. The error introduced is larger after oral administration as a result of marked first-pass metabolism of quinidine. The absolute oral bioavailabilities from pharmaceutical preparations might therefore be estimated higher in studies with assays including metabolites in the determination. Although the pharmacodynamic response to quinidine is related to the plasma concentration, the therapeutic window of drug concentrations has been defined only using nonspecific assays. In light of the availability of newly developed specific assays, redefinition of the range of therapeutic plasma concentrations is opportune.
先前发表的奎尼丁药代动力学特征估计值显示，其依赖于研究者是否使用了针对奎尼丁的分析方法。在使用无法区分奎尼丁与其代谢物的非特异性测定法的研究中，给药后的血浆浓度-时间曲线下面积和血浆峰浓度较高，因此清除率值较低。由于奎尼丁显著的首过代谢，口服给药后引入的误差更大。因此，在测定中包括代谢物的研究中，药物制剂的绝对口服生物利用度可能估计得更高。尽管对奎尼丁的药效学反应与血浆浓度有关，但药物浓度的治疗窗仅使用非特异性测定法定义。鉴于新开发的特异性测定法的可用性，适时重新定义治疗性血浆浓度范围是合适的。
