Fisher D M, Kahwaji R, Bevan D, Bikhazi G, Fragen R J, Angst M S, Ornstein E, Matteo R S
Department of Anesthesia, University of California, San Francisco 94143-0648, USA.
Anesthesiology. 1999 Apr;90(4):993-1000. doi: 10.1097/00000542-199904000-00011.
Rapacuronium is a new nondepolarizing muscle relaxant with rapid onset and offset. As part of a study to determine its neuromuscular effects, the authors sampled plasma sparsely to determine the influence of age, gender, and other covariates on its pharmacokinetic characteristics.
Of 181 patients receiving a single bolus dose of 0.5-2.5 mg/kg rapacuronium, 43 (aged 24-83 yr) had plasma sampled 3 or 4 times to determine plasma concentrations of rapacuronium and its metabolite, ORG9488. Pharmacokinetic analysis was performed using a population approach (mixed-effects modeling) to determine the influence of demographic characteristics and preoperative laboratory values on the pharmacokinetic parameters.
Rapacuronium's weight-normalized plasma clearance was 7.03 x (1 - 0.0507 x (HgB - 13)) ml x kg(-1) x min(-1), where HgB is the patient's preoperative value for hemoglobin (g/100 ml); however, rapacuronium's blood clearance (11.4+/-1.4 ml x kg(-1) x min(-1), mean +/- SD) did not vary with hemoglobin. Rapacuronium's weight-normalized pharmacokinetic parameters were not influenced by age, gender, or other covariates examined. Plasma concentrations of ORG9488 were typically less than 14% those of rapacuronium during the initial 30 min after rapacuronium administration.
In this patient population, neither age nor gender influence elimination of rapacuronium. This finding contrasts to an age-related decrease in plasma clearance observed in a study of 10 healthy volunteers and in a pooled analysis of the pharmacokinetic data from 206 adults in multiple clinical studies. Even if ORG9488 has a potency similar to that of rapacuronium, its plasma concentrations after a single bolus dose of rapacuronium are sufficiently small to contribute minimally to neuromuscular blockade.
瑞帕库溴铵是一种新型非去极化肌松药，起效快、作用消失也快。作为确定其神经肌肉效应研究的一部分，作者对血浆进行了稀疏采样，以确定年龄、性别和其他协变量对其药代动力学特征的影响。
在181例接受单次静脉推注剂量为0.5 - 2.5mg/kg瑞帕库溴铵的患者中，43例（年龄24 - 83岁）进行了3或4次血浆采样，以测定瑞帕库溴铵及其代谢产物ORG9488的血浆浓度。采用群体方法（混合效应建模）进行药代动力学分析，以确定人口统计学特征和术前实验室值对药代动力学参数的影响。
瑞帕库溴铵的体重标准化血浆清除率为7.03×(1 - 0.0507×(HgB - 13))ml·kg⁻¹·min⁻¹，其中HgB是患者术前血红蛋白值（g/100ml）；然而，瑞帕库溴铵的血液清除率（11.4±1.4ml·kg⁻¹·min⁻¹，均值±标准差）并不随血红蛋白而变化。瑞帕库溴铵的体重标准化药代动力学参数不受年龄、性别或所检查的其他协变量影响。在给予瑞帕库溴铵后的最初30分钟内，ORG9488的血浆浓度通常不到瑞帕库溴铵的14%。
在该患者群体中，年龄和性别均不影响瑞帕库溴铵的消除。这一发现与在10名健康志愿者的研究以及多项临床研究中对206名成年人药代动力学数据的汇总分析中观察到的与年龄相关的血浆清除率降低形成对比。即使ORG9488的效能与瑞帕库溴铵相似，单次静脉推注剂量的瑞帕库溴铵后其血浆浓度也足够低，对神经肌肉阻滞的贡献极小。
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