Wierda J M, Kleef U W, Lambalk L M, Kloppenburg W D, Agoston S
Research Group for Experimental Anesthesiology and Clinical Pharmacology, University of Groningen, The Netherlands.
Can J Anaesth. 1991 May;38(4 Pt 1):430-5. doi: 10.1007/BF03007578.
The pharmacodynamics and pharmacokinetics of a new non-depolarizing neuromuscular blocking agent, Org 9426, were investigated. Ten patients undergoing elective head and neck surgery and anaesthetized with nitrous oxide, halothane and fentanyl, received a bolus dose of Org 9426 (1 mg.kg-1, 3 x ED90). The isometric contractions of the adductor pollicis muscle following ulnar nerve stimulation (0.1 Hz and intermittent TOF) were measured. Blood and urine were sampled over 8 and 24 hr, respectively. Concentrations of Org 9426 and its possible metabolites in plasma and urine were determined using HPLC. Pharmacokinetic variables were calculated by iterative linear least square regression analysis. Intubation conditions were excellent one minute after administration at a neuromuscular block of 88 (13)% (Mean (CV]. Onset time until maximum block, duration until 25% recovery of twitch height, and recovery from 25 until 75% of twitch height were 1.7 (32), 53 (19) and 20 (37) min, respectively. The TOF reached a ratio of 0.7 after 87 (19) min. Half lives were 1.8 (33), 19 (34), 131 (62) min, respectively, in a three exponential decay; distribution volume at steady-state and plasma clearance were 0.264 (56) L.kg-1 and 4.0 (21) ml.kg-1.min-1, respectively. Plasma concentration at 25% recovery of the twitch height was 1.0 mg.L-1. Within 24 h, 33 (37)% of Org 9426 was excreted unchanged in the urine. Metabolites were absent both in plasma and urine. We conclude that the difference in potency between Org 9426 and vecuronium is similar to the difference between their effective concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
对一种新型非去极化神经肌肉阻滞剂Org 9426的药效学和药代动力学进行了研究。10例接受择期头颈手术并以氧化亚氮、氟烷和芬太尼麻醉的患者，接受了一剂Org 9426（1mg·kg-1，3倍ED90）。测量了尺神经刺激（0.1Hz和间歇性强直后计数）后拇内收肌的等长收缩。分别在8小时和24小时内采集血液和尿液样本。使用高效液相色谱法测定血浆和尿液中Org 9426及其可能代谢物的浓度。通过迭代线性最小二乘回归分析计算药代动力学变量。给药1分钟后，在神经肌肉阻滞为88（13）%（均值（变异系数））时插管条件极佳。直至最大阻滞的起效时间、直至颤搐高度恢复25%的持续时间以及从颤搐高度的25%恢复至75%的恢复时间分别为1.7（32）、53（19）和20（37）分钟。87（19）分钟后强直后计数比值达到0.7。在三指数衰减中，半衰期分别为1.8（33）、19（34）、131（62）分钟；稳态分布容积和血浆清除率分别为0.264（56）L·kg-1和4.0（21）ml·kg-1·min-1。颤搐高度恢复25%时的血浆浓度为1.0mg·L-1。24小时内，33（37）%的Org 9426以原形经尿液排泄。血浆和尿液中均未发现代谢物。我们得出结论，Org 9426和维库溴铵之间的效价差异与其有效浓度之间的差异相似。（摘要截短至250字）
