Brater D C, Leinfelder J, Anderson S A
Clin Pharmacol Ther. 1987 Aug;42(2):187-92. doi: 10.1038/clpt.1987.131.
Torasemide is a new loop diuretic that potentially may have renal tubular effects from both the blood and urinary sides of the nephron. We assessed its pharmacokinetics and pharmacodynamics in eight normal subjects administering intravenous doses of 5, 10, and 20 mg compared with 40 mg furosemide. We assessed the effect of probenecid on response to the 20 mg dose. A dose intermediate to the 10 and 20 mg doses appeared equally natriuretic to 40 mg furosemide. Although total clearance was the same with all doses (about 0.45 ml/min/kg), renal clearance and the fraction of unchanged drug appearing in the urine decreased with higher doses raising the question of saturable renal secretion. Urinary dose-response curves showed torasemide to be five times as potent as furosemide. Probenecid pretreatment decreased both urine volume (P = 0.0016) and sodium excretion (P = 0.0003), implying that delivery of drug to the urinary side of the nephron is the major determinant of response.
托拉塞米是一种新型袢利尿剂，可能在肾单位的血液和尿液两侧都具有肾小管效应。我们评估了8名正常受试者静脉注射5、10和20mg托拉塞米的药代动力学和药效学，并与40mg呋塞米进行比较。我们评估了丙磺舒对20mg剂量反应的影响。10mg和20mg剂量之间的一个中间剂量显示出与40mg呋塞米同样的利钠作用。尽管所有剂量的总清除率相同（约0.45ml/分钟/千克），但随着剂量增加，肾清除率和尿液中未变化药物的比例降低，这就提出了肾分泌饱和的问题。尿剂量反应曲线显示托拉塞米的效力是呋塞米的五倍。丙磺舒预处理降低了尿量（P = 0.0016）和钠排泄（P = 0.0003），这意味着药物输送到肾单位的尿液侧是反应的主要决定因素。
