Reynolds L M, Infosino A, Brown R, Hsu J, Fisher D M
Department of Anesthesia and Perioperative Care, University of California, San Francisco 94143-0648, USA.
Anesthesiology. 2000 Feb;92(2):376-86. doi: 10.1097/00000542-200002000-00018.
A nondepolarizing muscle relaxant with an onset and offset profile similar to succinylcholine is desirable for pediatric anesthesia. The onset and offset of rapacuronium are rapid in children. In the current study, the authors determined its pharmacokinetic characteristics in children. In addition to administering rapacuronium by the usual intravenous route, the authors also gave rapacuronium intramuscularly to determine uptake characteristics and bioavailability.
Forty unpremedicated patients aged 2 months to 3 yr were anesthetized with halothane, 0.82-1.0% end-tidal concentration. When anesthetic conditions were stable, rapacuronium was injected either into a peripheral vein (2 mg/kg for infants, 3 mg/kg for children) or a deltoid muscle (2.8 mg/kg for infants, 4.8 mg/kg for children). Four venous plasma samples were obtained from each subject 2-240 min after rapacuronium administration. A mixed-effects population pharmacokinetic analysis was applied to these values to determine bioavailability, absorption rate constant, and time to peak plasma concentration with intramuscular administration.
Plasma clearance was 4.77 ml x kg(-1) x min(-1) + 8.48 ml/min. Intramuscular bioavailability averaged 56%. Absorption from the intramuscular depot had two rate constants: 0.0491 min(-1) (72.4% of absorbed drug) and 0.0110 min(-1) (27.6% of the absorbed drug). Simulation indicated that plasma concentration peaks 4.0 and 5.0 min after intramuscular rapacuronium in infants and children, respectively, and that, at 30 min, less than 25% of the administered dose remains to be absorbed from the intramuscular depot.
In infants and children, rapacuronium's clearance and steady state distribution volume are less than in adults. After intramuscular administration, bioavailability is 56%, and plasma rapacuronium concentrations peak within 4 or 5 min.
对于小儿麻醉而言，需要一种起效和消退时间与琥珀酰胆碱相似的非去极化肌松药。瑞帕库溴铵在儿童中的起效和消退迅速。在本研究中，作者测定了其在儿童中的药代动力学特征。除了通过常用的静脉途径给予瑞帕库溴铵外，作者还通过肌肉注射给予瑞帕库溴铵以确定摄取特征和生物利用度。
40例年龄在2个月至3岁之间未使用术前药的患儿，采用0.82 - 1.0%呼气末浓度的氟烷进行麻醉。当麻醉条件稳定时，将瑞帕库溴铵注入外周静脉（婴儿2 mg/kg，儿童3 mg/kg）或三角肌（婴儿2.8 mg/kg，儿童4.8 mg/kg）。在给予瑞帕库溴铵后2 - 240分钟，从每个受试者采集4份静脉血浆样本。对这些数值进行混合效应群体药代动力学分析，以确定肌肉注射给药时的生物利用度、吸收速率常数和血浆浓度达峰时间。
血浆清除率为4.77 ml·kg⁻¹·min⁻¹ + 8.48 ml/min。肌肉注射的生物利用度平均为56%。从肌肉注射部位的吸收有两个速率常数：0.0491 min⁻¹（占吸收药物的72.4%）和0.0110 min⁻¹（占吸收药物的27.6%）。模拟表明，婴儿和儿童肌肉注射瑞帕库溴铵后血浆浓度分别在4.0和5.0分钟达到峰值，并且在30分钟时，给药剂量中不到25%仍有待从肌肉注射部位吸收。
在婴儿和儿童中瑞帕库溴铵的清除率和稳态分布容积低于成人。肌肉注射给药后，生物利用度为56%，血浆瑞帕库溴铵浓度在4或5分钟内达到峰值。
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