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目的 :探讨盐酸普罗帕酮 (PPF)旋光异构体在人体内是否存在立体选择性相互作用及其作用规律。方法 :以 2、3-二对甲苯甲酰酒石酸为拆分试剂 ,得到单纯旋光异构体 (R) -PPF和 (S) -PPF ;建立以GITC柱前衍生化反相HPLC测定血浆中两旋光异构体浓度的方法。随机双盲 ,交叉给药 ,测定 8名健康受试者多次口服等剂量的 (R/S) -PPF·HCl、(S) -PPF·HCl、(R)-PPF·HCl及安慰剂片达稳态后的一个给药间隔的药时数值 ,计算药代动力学参数 ,比较以消旋体和以单纯旋光异构体给药的药动学参数。结果 :以消旋体给药 ,(R) -PPF竞争性抑制 (S) -PPF体内消除 ,使两旋光异构体Cl ,AUC和Css/D值与以单纯旋光异构体给药的值相比 ,有显著性改变。结论 :盐酸普罗帕酮旋光异构体在人体内存在立体选择性相互作用 ,为临床合理应用手性药物提供新的理论依据。
Objective: To investigate whether stereoselective interaction of propafenone hydrochloride (PPF) optical isomers and its action pattern exist in human. Methods: The pure optical isomers (R) -PPF and (S) -PPF were obtained by using 2,3-di-p-toluyl tartaric acid as the resolution reagent. Method of optical isomer concentration. (R / S) -PPF · HCl, (S) -PPF · HCl, (R) -PPF · HCl, and placebo tablets were orally administered to eight healthy subjects on multiple occasions Pharmacokinetic parameters were calculated at one dosing interval after steady state was reached, and the pharmacokinetic parameters were compared for racemate and pure optical isomer. Results: Administration of (R) -PPF competitively inhibits in vivo elimination of (S) -PPF by racemic administration, making the values of the Cl, AUC and Css / D of the two optical isomers correspond to the value of the optical isomer Compared to a significant change. CONCLUSION: Propafenone hydrochloride optical isomer has stereoselective interaction in human body, providing a new theoretical basis for the clinical rational use of chiral drugs.