Jounela A J, Pentikäinen P J, Oksanen K
Int J Clin Pharmacol Ther Toxicol. 1982 Jun;20(6):276-82.
The effects of acute myocardial infarction on the pharmacokinetics of disopyramide were studied. Disopyramide (200 mg) was given orally to nine patients with left-sided cardiac failure due to acute myocardial infarction within 24 h after the onset (phase I). In seven patients the study was repeated 7-14 days later at discharge from the hospital (phase II). Serum concentrations and the 24-h area under the serum concentration-time curve of disopyramide were significantly lower during phase I than during phase II (p less than 0.05 and p less than 0.001, respectively). The peak serum concentrations and the 24-h area under the pulmonary capillary wedge pressure (less than 0.05) in phase I. Rates of absorption and elimination of disopyramide were similar during both phases. Renal clearance of disopyramide showed concentrations and the decrease of 24-h area under the serum concentration-time curve are most probably due to decreased gastrointestinal absorption and are related to the degree of left ventricular failure. Thus, the dosage of oral disopyramide obviously needs to be increased in these patients to achieve therapeutic concentrations in the acute phase.
研究了急性心肌梗死对丙吡胺药代动力学的影响。在急性心肌梗死发作后24小时内,对9例因急性心肌梗死导致左侧心力衰竭的患者口服丙吡胺(200毫克)(第一阶段)。7例患者在出院后7 - 14天重复该研究(第二阶段)。丙吡胺的血清浓度及血清浓度-时间曲线下24小时面积在第一阶段显著低于第二阶段(分别为p < 0.05和p < 0.001)。第一阶段血清峰值浓度及肺毛细血管楔压下24小时面积降低(< 0.05)。两个阶段丙吡胺的吸收和消除速率相似。丙吡胺的肾清除率显示,血清浓度及血清浓度-时间曲线下24小时面积的降低很可能是由于胃肠道吸收减少,且与左心室衰竭程度有关。因此,这些患者口服丙吡胺的剂量在急性期明显需要增加以达到治疗浓度。