Brater D C, Rudy D R, Voelker J R, Greene P K, Gehr T, Sica D A
Department of Medicine, Indiana University School of Medicine, Indianapolis.
Cardiovasc Drugs Ther. 1993 Jan;7 Suppl 1:69-73. doi: 10.1007/BF00877960.
The pharmacokinetics and pharmacodynamics of torasemide were studied in 24 subjects with chronic renal insufficiency. The subjects were divided into two groups of patients, half having a creatinine clearance < 30 ml/min and the other half having a creatinine clearance between 30 and 60 ml/min. Three different intravenous doses were studied in each patient group. Pharmacokinetic analysis revealed dose proportionality when relating area under the concentration curve to dose. There was a progressive decrease in renal clearance of torasemide with declining renal function. In contrast, there was no difference in serum elimination half-life among the patients. In addition, this half-life was not different from that observed in healthy young or elderly control subjects. In previous reports on patients with congestive heart failure and liver disease, serum half-life values were prolonged compared to that of control subjects, presumably due to decreased hepatic, nonrenal clearance of torasemide. Supportive of this hypothesis is the considerably increased area under the serum vs. concentration time curve in such patients. In summary, this study has shown that the serum half-life of torasemide would be unchanged in patients with renal disease. The ceiling dose for torasemide (i.e., the dose above which no further drug-induced natriuresis is obtained) has been preliminarily found to be a single 100-mg intravenous dose in patients with moderate renal insufficiency and a single 200-mg intravenous dose in patients with severe disease.
在24例慢性肾功能不全患者中研究了托拉塞米的药代动力学和药效学。这些患者被分为两组，一组肌酐清除率<30 ml/分钟，另一组肌酐清除率在30至60 ml/分钟之间。在每个患者组中研究了三种不同的静脉给药剂量。药代动力学分析显示，浓度曲线下面积与剂量相关时呈剂量比例关系。随着肾功能下降，托拉塞米的肾清除率逐渐降低。相比之下，患者之间的血清消除半衰期没有差异。此外，该半衰期与健康年轻或老年对照受试者中观察到的半衰期没有差异。在先前关于充血性心力衰竭和肝病患者的报告中，血清半衰期值与对照受试者相比延长，推测是由于托拉塞米的肝脏非肾清除率降低。支持这一假设的是此类患者血清与浓度时间曲线下面积显著增加。总之，本研究表明，肾病患者中托拉塞米的血清半衰期将保持不变。托拉塞米的最大剂量（即超过该剂量不再获得药物诱导的利钠作用）初步发现，中度肾功能不全患者为单次静脉注射100 mg，重度疾病患者为单次静脉注射200 mg。
