Vozeh S, Uematsu T, Guentert T W, Ha H R, Follath F
Clin Pharmacol Ther. 1985 May;37(5):575-81. doi: 10.1038/clpt.1985.90.
3-OH-quinidine, a major quinidine metabolite, has been reported to have antiarrhythmic activity in animals and is suspected to contribute to the effect of quinidine in man. Four healthy subjects received 3-OH-quinidine in increasing oral doses (35, 100, 300 mg) to achieve serum concentrations in the range of those after quinidine dosing in patients. Blood and urine were collected up to 48 hours and blood pressure, heart rate, and averaged ECG complexes were recorded during 12 hours after dosing. Kinetic analysis revealed differences from published data for the parent drug. Renal clearance was 16 L/hr. The elimination t1/2 was 12.4 hours, substantially longer than that of quinidine. No systematic ECG changes were observed in two subjects with maximum concentrations of 55 and 215 micrograms/L. In the other two subjects who achieved higher maximum concentrations (447 and 918 micrograms/L), there was a significant relationship between the length of the corrected QT interval and the serum concentration of 3-OH-quinidine. These first dynamic results indicate that 3-OH-quinidine exerts effects in man resembling those of quinidine and may contribute to the antiarrhythmic activity of quinidine.
3-羟基奎尼丁是奎尼丁的主要代谢产物，据报道它在动物体内具有抗心律失常活性，并且被怀疑对奎尼丁在人体内的作用有贡献。四名健康受试者口服递增剂量（35、100、300毫克）的3-羟基奎尼丁，以达到患者服用奎尼丁后血清浓度范围。在给药后48小时内收集血液和尿液，并在给药后12小时内记录血压、心率和平均心电图复合波。动力学分析显示与已发表的母体药物数据存在差异。肾清除率为16升/小时。消除半衰期为12.4小时，明显长于奎尼丁。在两名最大浓度分别为55和215微克/升的受试者中未观察到系统性心电图变化。在另外两名达到更高最大浓度（447和918微克/升）的受试者中，校正QT间期的长度与3-羟基奎尼丁的血清浓度之间存在显著关系。这些初步的动力学结果表明，3-羟基奎尼丁在人体内产生的作用类似于奎尼丁，可能对奎尼丁的抗心律失常活性有贡献。
