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采用随机、交叉、双盲法给予8名健康受试者多次剂量(150 mg q6h)来考察普罗帕酮三种片剂(消旋体、左旋体、右旋体)和安慰剂,立体选择性高效液相色谱法测定稳态时一个给药间隔(0-6h)的血浆中两对映体浓度,心电图同时记录PR、QRS和QTc间隙并测试最大运动心率HRmax及血压变化情况,TopFit软件拟合参数。结果表明,三种制剂的平均驻留时间MRT及峰时Tmax无差别。给予消旋体片剂后,右旋体的清除率C1明显低于左旋体(P<0.05),单纯给予对映体时,右旋体的清除率则大于左旋体(P<0.001)。左旋体的存在提高了右旋体的血浆浓度,增强了β一受体阻断作用。普罗帕酮在人体内消除存在立体选择性,且两对映体产生了药效学上的相互作用。临床应用消旋体可不作剂量调整,但对某些患者应慎重使用。
A randomized, crossover, double-blind trial of three doses of propafenone (racemate, levorotary, dex) and placebo in multiple doses of eight healthy subjects (150 mg q6h) The two enantiomers in plasma at steady-state intervals (0-6h) were measured by HPLC. The electrocardiograms were recorded simultaneously with PR, QRS and QTc gaps and the maximum exercise heart rate (HRmax) and blood pressure were measured. TopFit software Fitting parameters. The results showed that the average residence time of the three formulations MRT and peak Tmax no difference. After administration of racemic tablets, the clearance rate of dextromethorphan C1 was significantly lower than that of levomyosis (P <0.05). When the enantiomers were administered alone, the clearance rate of dextromethorphan was higher than that of levaris (P <0.05). 001). The presence of levorotatory increases the plasma concentration of dextromethorphan and enhances the blockade of beta -receptor. Propafenone eliminates the stereoselectivity in the human body and the two enantiomers have pharmacodynamic interactions. Clinical application of racemate may not be dose-adjusted, but should be used with caution in some patients.