McErlane K M, Igwemezie L, Kerr C R
Res Commun Chem Pathol Pharmacol. 1987 Apr;56(1):141-4.
The binding of mexiletine enantiomers to human serum proteins was studied in vitro using serum samples collected from five healthy male subjects. Racemic mexiletine was added to an aliquot of each subject's serum to cover the concentration range 0.2 to 2.0 micrograms/mL. Following ultrafiltration of the serum samples containing racemic mexiletine, the individual enantiomers were determined using a stereoselective high-performance liquid chromatographic method developed in our laboratory. The assay data thus obtained for the free levels of the enantiomers showed that the free fraction of S(+) mexiletine was 28.32 +/- 1.45% and that of the R(-) enantiomer was 19.80 +/- 1.49%. The binding was shown to be significantly greater (p less than 0.001) for R(-) mexiletine than its antipode. There was no evidence of concentration dependence in binding over the concentration range studied, which covered the normal therapeutic range. However, significant inter-individual variability in the free fractions was observed. The total binding of the enantiomers was 76%.
使用从五名健康男性受试者采集的血清样本，在体外研究了美西律对映体与人血清蛋白的结合情况。将消旋美西律添加到每个受试者血清的一份等分试样中，使其浓度范围涵盖0.2至2.0微克/毫升。在对含有消旋美西律的血清样本进行超滤后，使用我们实验室开发的立体选择性高效液相色谱法测定各个对映体。由此获得的对映体游离水平的测定数据表明，S(+)美西律的游离分数为28.32±1.45%，R(-)对映体的游离分数为19.80±1.49%。结果显示，R(-)美西律的结合力显著高于其对映体（p<0.001）。在所研究的涵盖正常治疗范围的浓度范围内，未发现结合存在浓度依赖性。然而，观察到游离分数存在显著的个体间差异。对映体的总结合率为76%。
