Giani P, Landolina M, Giudici V, Bianchini C, Ferrario G, Marchi S, Riva E, Latini R
Divisione di Cardiologia, Seriate (Bergamo), Italy.
Eur J Clin Pharmacol. 1988;34(2):187-94. doi: 10.1007/BF00614557.
The pharmacokinetics of propafenone and 5-OH-propafenone and their relationship with the antiarrhythmic action and side effects have been studied in 10 patients with stable, frequent, premature ventricular beats (224-928 premature ventricular complexes/h). Observations were made after a single dose of propafenone 300 mg p.o., and after 1 and 3 months (only 5 out of 10 patients) of therapy with 300 mg t.d.s. After 1 month of treatment the plasma elimination half-life of propafenone (6.7 h) was almost twice as long as after a single dose (3.5 h), and the area under the plasma propafenone concentration-time curve (7620 ng.ml-1.h) was significantly larger than after single dose (3522 ng.ml-1.h); this was also true for the metabolite. The ratio of the AUCs of 5-OH-propafenone and propafenone decreased from the single dose (0.63) to 1 month (0.32). These variables remained stable up to 3 months. Eight patients had greater than or equal to 75% reduction of premature ventricular complexes after 3 days of therapy, and in 7 they were completely suppressed; the response was maintained over 1 to 3 months. Side effects were minor and in no case had the drug to be withdrawn or the dose reduced. Thus, the kinetics of propafenone were time-dependent. Its active metabolite did not accumulate greatly during chronic treatment. The lasting antiarrhythmic effect observed in some patients suggests a b.d.s. regimen instead of t.d.s. dosing in selected patients.
对10例患有稳定、频发室性早搏（每小时224 - 928次室性早搏）的患者，研究了普罗帕酮和5 - 羟基普罗帕酮的药代动力学及其与抗心律失常作用和副作用的关系。在口服单剂量300 mg普罗帕酮后，以及在每日3次、每次300 mg治疗1个月和3个月后（10例患者中仅5例）进行观察。治疗1个月后，普罗帕酮的血浆消除半衰期（6.7小时）几乎是单剂量后（3.5小时）的两倍，血浆普罗帕酮浓度 - 时间曲线下面积（7620 ng·ml⁻¹·h）显著大于单剂量后（3522 ng·ml⁻¹·h）；代谢产物的情况也是如此。5 - 羟基普罗帕酮与普罗帕酮的AUC比值从单剂量时的0.63降至1个月时的0.32。这些变量在3个月内保持稳定。8例患者在治疗3天后室性早搏减少了75%或更多，7例患者的室性早搏完全被抑制；这种反应在1至3个月内持续存在。副作用轻微，无一例需要停药或减量。因此，普罗帕酮的药代动力学具有时间依赖性。其活性代谢产物在慢性治疗期间没有大量蓄积。在一些患者中观察到的持久抗心律失常作用提示在选定患者中采用每日两次的给药方案而非每日三次给药。
