Miller R D, Matteo R S, Benet L Z, Sohn Y J
J Pharmacol Exp Ther. 1977 Jul;202(1):1-7.
Plasma and urine concentrations of d-tubocurarine (d-TC) were determined and twitch tension was monitored before and after the intravenous administration of d-TC, 0.5 mg/kg in patients anethetized with halothane and nitrous oxide with (N=5) and without (N=5) renal failure. Terminal half lives of d-TC of 231 and 330 minutes predicted from other studies for patients with and without renal function were consistent with plasma concentrations measured. In patients with normal renal function, 38% of unchanged d-TC was eliminated in urine in 25 hours as opposed to 13% in those patients with a newly transplanted kidney. However, we still conclude that a newly transplanted kidney can eliminate d-TC effectively since the kidney was inserted 3.5 hours after administration of d-TC. Absence of renal function significantly prolonged the duration of neuromuscular blockade but did not alter the plasma concentrations of d-TC required for neuromuscular blockade. Thus, prolonged neuromuscular blockade from d-TC in patients with renal failure is due to decreased elimination rate of the drug as a consequence of lack of renal function rather than increased sensitivity.
测定了d-筒箭毒碱(d-TC)的血浆和尿液浓度,并在静脉注射0.5mg/kg d-TC前后监测了肌肉抽搐张力,这些患者接受了氟烷和氧化亚氮麻醉,其中5例有肾衰竭,5例无肾衰竭。根据其他研究预测,有和没有肾功能的患者d-TC的终末半衰期分别为231分钟和330分钟,这与所测血浆浓度一致。在肾功能正常的患者中,25小时内有38%未变化的d-TC经尿液排出,而在新移植肾脏的患者中这一比例为13%。然而,我们仍然得出结论,新移植的肾脏能够有效清除d-TC,因为在注射d-TC 3.5小时后植入了肾脏。肾功能缺失显著延长了神经肌肉阻滞的持续时间,但并未改变神经肌肉阻滞所需的d-TC血浆浓度。因此,肾衰竭患者中d-TC导致的神经肌肉阻滞延长是由于缺乏肾功能导致药物清除率降低,而非敏感性增加。