Schwartz S, Brater D C, Pound D, Green P K, Kramer W G, Rudy D
Boehringer Mannheim Pharmaceuticals, Inc., Rockville.
Clin Pharmacol Ther. 1993 Jul;54(1):90-7. doi: 10.1038/clpt.1993.116.
The bioavailability, pharmacokinetics, and pharmacodynamics of torsemide (10 mg orally and intravenously) were determined in a randomized crossover clinical trial with 12 patients with ascites caused by cirrhosis. Torsemide was rapidly absorbed with a bioavailability of 96.3% (confidence interval, 84% to 109%). Compared with healthy subjects, patients with cirrhosis exhibit a decrease in nonrenal clearance and increases in bioavailability, volume of distribution, renal clearance, elimination half-life, and percentage of the dose excreted into the urine. A greater proportion of the dose is delivered to the site of action over a more prolonged period of time. In spite of a shift of the pharmacodynamic curve to the right in patients with cirrhosis, there was no significant difference in natriuresis. Pharmacokinetic changes of torsemide in cirrhosis therefore compensate for the pharmacodynamic abnormality.
在一项针对12例肝硬化腹水患者的随机交叉临床试验中，测定了托拉塞米（口服和静脉注射10毫克）的生物利用度、药代动力学和药效学。托拉塞米吸收迅速，生物利用度为96.3%（置信区间为84%至109%）。与健康受试者相比，肝硬化患者的非肾清除率降低，生物利用度、分布容积、肾清除率、消除半衰期以及尿中排泄剂量的百分比增加。更大比例的剂量在更长的时间内输送到作用部位。尽管肝硬化患者的药效学曲线向右移动，但利钠作用没有显著差异。因此，托拉塞米在肝硬化中的药代动力学变化可补偿药效学异常。
