缓释剂长效盐酸二氢奎尼丁药物动力学和药效学的初步研究

对服用缓释剂长效盐酸二氢奎尼丁（Ｓｅｒｅｃｏｒ，赛利科）的８例健康者及３１例心律失常患者，采用反相高效液相色谱法检测血药浓度，用Ｈｏｌｔｅｒ评判疗效，以研究口服Ｓｅｒｅｃｏｒ后的药物动力学和药效学。研究表明：①健康者单剂量口服和心律失常患者多剂量口服达稳态时药－时曲线均符合一室开放模型。②口服Ｓｅｒｅｃｏｒ后，抗室性和房性心律失常的总有效率分别为８８．９％和７５．０％，慢性心房颤动（简称房颤）的复律成功率为５０．０％。最低平均有效血药浓度：抗室性心律失常为０．７１μｇ／ｍｌ、抗房性心律失常为１．１６μｇ／ｍｌ、慢性房颤复律为１．９２μｇ／ｍｌ。发生促心律失常作用的血药浓度为２．２９μｇ／ｍｌ。不良反应发生率为３２．３％，其中以胃肠道反应多见。结论：口服Ｓｅｒｅｃｏｒ后吸收较快，稳态时药－时曲线稳定性和缓和性均较理想，每１２ｈ给药一次的方式是合理的。Ｓｅｒｅｃｏｒ对室性和房性心律失常均有效，但抗室性心律失常疗效优于房性心律失常。

A Primary Study of Pharmacokinetics and Pharmacodynamics of Slow Released, Long Action Chlorhydric Dihydroquinidine

The plasma concentration of slow released,long action chlorhydric dihydroquinidine (Serecor) was measured by a reversed phase high performance liquids chromatography (RP HPLC) in 8 healthy volunteers and in 31 patients with arrhythmias after oral Serecor.The efficiency was evaluated by Hotler monitoring in the patients and the pharmacokinetics and pharmacodynamics of Serecor were investigated.The results showed:(1)The CT data of Serecor were fit to one compartmental model at steady state both in the healthy volunteers after oral a single dose of Serecor and in the patients after several Serecor.(2)The total efficacy rate after oral Serecor in treatment of ventricular arrhythmias,supraventricular arrhythmias and chronic atrial fibrillation (Af) which was converted to sinus rhythm were separately 88.9%,75.0%,and 50.0%.The mean therapeutic plasma concentration for ventricular arrhythmias,supraventricular arrhythmias and chronic Af were separately 0.71 μg/ml,1.16 μg/ml and 1.92 μg/ml.The plasma concentration of proarrhythmic effects was 2.29 μg/ml.The side effect rate was 32.3%.The frequency of gastrointestinal side effects was higher.Conclusion:To absorb quickly in oral Serecor.The stability and fluctuation of the CT data were satisfactory.The method of taking serecor per 12 hours was correct.Serecor is a useful agent in treatment of ventricular arrhythmias,supraventricular arrhythmias.The efficacy of oral Serecor for ventricular arrhythmias was better than for supraventricular arrhythmias.