摘要
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。
Eight healthy male subjects received treatment in a randomized, cross-over, double-blind study R/S-,S- and R- propafenone in multiple doses (150 mg each every 6 h) and placebo. The steady state plasma concentrations of both enantiomers of propafenone in the last dose interval were measured by stereoselective HPLC method and ECG, blood pressure and heart rate were monitored. Pharmacokinetic parameters were calculated by the TopFit programe. The data indicated that mean residence time(MRT) and time to reach peak concentrations(Tmax) of S- and R-propafenone were similar and independent of the administered agent. When the racemate was given, the clearance of S- propafenone was lower than that of R- propafenone(p<0.05). When the pure enantiomer was administrated alone, the clearance of S- propafenone was higher than that of R- propafenone(p<0.00l). The plasma concentrations of S- propafenone were higher in the presence of R- propafenone and β - adrenoceptor blocking action of S- propafenone was affected by the presence of its optical antipode. A stereoselective elimination of propafenone was observed in chinese subjects. Enantiomer/enantiomer interaction in pharmacokinetics and pharmacodynamics was also occurred. Dosage modifications are probably not required in patients receiving racemic propafenone, but it must be used cautiously for some treatment of arrhythmia.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2000年第1期31-35,共5页
The Chinese Journal of Clinical Pharmacology
