Masuhara K, Ohno T, Hamaguchi K, Katoh K, Kashiwada K, Takahashi S, Tanaka Y, Someya K, Ogata H
Department of Pharmacy, St. Marianna University, Kanagawa, Japan.
Int J Clin Pharmacol Res. 1995;15(3):103-13.
After we had developed a method to determine simultaneously the blood concentrations of disopyramide (DP) and its metabolite mono-N-dealkylated disopyramide (MND) by high-performance liquid chromatography, DP was administered repeatedly to arrhythmic patients in order to examine the relationship between the serum DP or MND concentration and the therapeutic effects or side-effects. To 79 arrhythmic patients (57 patients with ventricular premature contraction, 13 with supraventricular arrhythmia and 9 with atrial fibrillation), DP was administered repeatedly at an initial oral dose of 200 to 400 mg/day. Of the 61 patients which were possible to evaluate after reaching a steady state, 32 were evaluated as effective and 29 as non-effective, the effective rate being 52.5%; the mean blood DP concentration (+/- S.D.) was 2.14 +/- 0.65 and 1.74 +/- 0.62 micrograms/ml, respectively, with a significant difference between the two groups (p +/- 0.05). At the final dose, 40 patients were evaluated as effective and 18 as non-effective, the effective rate being 69.0%; the mean blood DP concentration was 2.03 +/- 0.67 and 2.09 +/- 0.68 micrograms/ml, respectively, with no significant difference between the two groups. Among 42 patients with premature contraction, 26 were evaluated as effective and 16 as non-effective, the effective rate being 62%; the mean blood DP concentration was 2.01 +/- 0.62 and 2.20 +/- 0.70 micrograms/ml respectively, with no significant difference between the two groups. The incidence of side-effects was 17.7%, and there were no significant differences in blood DP or MND concentrations between the groups with and without side-effects. A blood DP concentration more than 2 micrograms/ml may be required to achieve the therapeutic effect of DP administered repeatedly.
我们开发出一种通过高效液相色谱法同时测定丙吡胺（DP）及其代谢产物单 - N - 去烷基丙吡胺（MND）血药浓度的方法后，为研究血清DP或MND浓度与治疗效果及副作用之间的关系，对心律失常患者反复给予DP。对79例心律失常患者（57例室性早搏、13例室上性心律失常和9例房颤患者），初始口服剂量为200至400mg/天，反复给予DP。在61例达到稳态后可评估的患者中，32例评估为有效，29例评估为无效，有效率为52.5%；两组的平均血DP浓度（±标准差）分别为2.14±0.65和1.74±0.62μg/ml，两组间有显著差异（p±0.05）。在最终剂量时，40例评估为有效，18例评估为无效，有效率为69.0%；两组的平均血DP浓度分别为2.03±0.67和2.09±0.68μg/ml，两组间无显著差异。在42例早搏患者中，26例评估为有效，16例评估为无效，有效率为62%；两组的平均血DP浓度分别为2.01±0.62和2.20±0.70μg/ml，两组间无显著差异。副作用发生率为17.7%，有副作用组和无副作用组之间的血DP或MND浓度无显著差异。反复给予DP可能需要血DP浓度超过2μg/ml才能达到治疗效果。
