Pentikäinen P J, Huikuri H, Jounela A J, Wilen G
Eur J Clin Pharmacol. 1985;28(1):45-51. doi: 10.1007/BF00635707.
To study the effects of acute myocardial infarction on the pharmacokinetics of disopyramide a single oral dose of disopyramide base (200 mg) was administered to 6 patients with myocardial infarction both in the acute (Study I) and recovery (Study II) phases. An intravenous tracer dose of 14C-disopyramide (2.5 micrograms/0.3 mg) was given simultaneously with the oral dose. On the basis of the intravenous tracer data, the volume of distribution, binding to plasma proteins, total plasma clearance, renal clearance and elimination half-life of disopyramide and mono-N-dealkyl disopyramide were the same in Studies I and II. The peak serum concentrations of disopyramide after oral dosing in Studies I and II were 2.6 +/- 1.2 (SEM) and 6.4 +/- 1.9 microgram/ml, respectively (p less than 0.05), the peak times 3.29 +/- 1.22 and 1.21 +/- 0.39 h (N.S.) and the AUCINF 38.0 +/- 7.7 and 60.7 +/- 9.9 micrograms . h . ml-1 (p less than 0.05). The recovery of disopyramide in urine over 3 days averaged 46% and 47% of dose, and that of mono-N-dealkyl disopyramide 22% and 16% of the dose, respectively. Thus, the gastrointestinal absorption of disopyramide was disturbed, resulting in low plasma concentrations after oral dosing, whereas the elimination of disopyramide was unaltered in the acute phase of myocardial infarction.
为研究急性心肌梗死对丙吡胺药代动力学的影响，对6例处于急性（研究I）和恢复（研究II）期的心肌梗死患者单次口服丙吡胺碱（200mg）。静脉注射示踪剂量的14C-丙吡胺（2.5μg/0.3mg）与口服剂量同时给予。根据静脉示踪数据，研究I和研究II中丙吡胺及单-N-去烷基丙吡胺的分布容积、与血浆蛋白的结合、总血浆清除率、肾清除率及消除半衰期相同。研究I和研究II中口服给药后丙吡胺的血清峰浓度分别为2.6±1.2（SEM）和6.4±1.9μg/ml（p<0.05），达峰时间分别为3.29±1.22和1.21±0.39h（无显著性差异），AUCINF分别为38.0±7.7和60.7±9.9μg·h·ml-1（p<0.05）。3天内尿中丙吡胺的回收率平均分别为给药剂量的46%和47%，单-N-去烷基丙吡胺的回收率分别为给药剂量的22%和16%。因此，丙吡胺的胃肠道吸收受到干扰，导致口服给药后血浆浓度较低，而在心肌梗死急性期丙吡胺的消除未改变。
