Baldwin K A, Forney R
Ventura County Sheriff's Criminalistics Laboratory, CA.
J Forensic Sci. 1988 Mar;33(2):470-9.
The study was undertaken to determine the pharmacokinetic values for half-life, volume of distribution, and clearance for succinylcholine (SCh) based on measurements of the drug in plasma. Three intravenous (i.v.) doses (0.5, 1.0, and 5.0 mg/kg) were compared to study the time course of paralysis and recovery and to describe the relationship of plasma concentration (Cp) and the pharmacologic effects of SCh in canines. The physiologic response to the neuromuscular blocking drug was monitored using train-of-four stimulation of the left sciatic nerve and recording the response of the corresponding gastrocnemius muscle. Time courses for paralysis and recovery were monitored, and the results were used to predict the kinetic values for the pharmacologic effects. Blood samples were taken following drug administration for direct pharmacokinetic estimations. SCh determinations were performed using ion-pair extraction, chemical demethylation, and gas chromatography with nitrogen phosphorous detection. Both kinetic analyses showed the beta half-life for SCh to be approximately 5 min for all doses. SCh has a distribution half-life of less than 1 min. There appears to be a threshold Cp below which neuromuscular function returns. Recovery following SCh induced paralysis had a rapid onset, but the duration of paralysis and the rate of recovery were especially prolonged for the 5.0-mg/kg treatment group.
本研究旨在根据血浆中药物的测量结果，确定琥珀酰胆碱（SCh）的半衰期、分布容积和清除率等药代动力学值。比较了三种静脉注射剂量（0.5、1.0和5.0mg/kg），以研究犬类中麻痹和恢复的时间过程，并描述血浆浓度（Cp）与SCh药理作用之间的关系。使用对左坐骨神经的四个成串刺激并记录相应腓肠肌的反应，来监测对神经肌肉阻滞药物的生理反应。监测麻痹和恢复的时间过程，并将结果用于预测药理作用的动力学值。给药后采集血样进行直接药代动力学估计。使用离子对萃取、化学脱甲基和带氮磷检测的气相色谱法进行SCh测定。两种动力学分析均显示，所有剂量的SCh的β半衰期约为5分钟。SCh的分布半衰期小于1分钟。似乎存在一个阈值Cp，低于该值神经肌肉功能会恢复。SCh诱导麻痹后的恢复起效迅速，但对于5.0mg/kg治疗组，麻痹持续时间和恢复速率尤其延长。
