Martin D E, Shen J, Griener J, Raasch R, Patterson J H, Cascio W
University of North Carolina, Chapel Hill, USA.
J Clin Pharmacol. 1996 Jan;36(1):85-91. doi: 10.1002/j.1552-4604.1996.tb04156.x.
Procainamide is a class I antiarrhythmic agent that undergoes active tubular secretion through the organic cation transport system, with approximately 50% of a dose excreted in the urine as unchanged drug. The remainder is metabolized to an active metabolite, n-acetyl procainamide (NAPA). Ofloxacin is a fluoroquinolone antibiotic that is excreted in the urine as unchanged drug via active tubular secretion and glomerular filtration. To test the hypothesis that ofloxacin may interfere with the renal elimination of procainamide, 9 healthy volunteers were randomly assigned to receive 1 g of oral procainamide as a single dose with or without pretreatment with 400 mg of ofloxacin twice a day for 5 doses. Blood and urine samples were obtained and pharmacokinetic parameters for procainamide were determined for each treatment period. Standard 12-lead and signal-averaged electrocardiographic recordings were used for pharmacodynamic analysis. The mean area under the concentration-time curve (AUC) and peak plasma concentration (Cmax; mug/mL) for procainamide increased by 27% and 21%, respectively, and the plasma clearance for procainamide decreased by an average of 22% with coadministration of ofloxacin. Ofloxacin did not significantly influence the pharmacokinetics of NAPA, nor were pharmacodynamics of procainamide significantly affected by coadministration of ofloxacin. These results suggest that procainamide concentrations should be monitored closely when coadministered with ofloxacin.
普鲁卡因胺是一种Ⅰ类抗心律失常药，通过有机阳离子转运系统进行主动肾小管分泌，约50%的剂量以原形药物经尿液排出。其余部分代谢为活性代谢产物N - 乙酰普鲁卡因胺（NAPA）。氧氟沙星是一种氟喹诺酮类抗生素，通过主动肾小管分泌和肾小球滤过以原形药物经尿液排出。为了验证氧氟沙星可能干扰普鲁卡因胺肾排泄的假说，9名健康志愿者被随机分为两组，一组单次口服1g普鲁卡因胺，另一组在每天两次口服400mg氧氟沙星共5剂进行预处理后，再单次口服1g普鲁卡因胺。采集血样和尿样，并测定每个治疗期普鲁卡因胺的药代动力学参数。采用标准12导联和信号平均心电图记录进行药效学分析。与氧氟沙星合用时，普鲁卡因胺的平均浓度 - 时间曲线下面积（AUC）和血浆峰浓度（Cmax；μg/mL）分别增加了27%和21%，普鲁卡因胺的血浆清除率平均降低了22%。氧氟沙星对NAPA的药代动力学没有显著影响，氧氟沙星与普鲁卡因胺合用对其药效学也没有显著影响。这些结果表明，与氧氟沙星合用时应密切监测普鲁卡因胺的浓度。
