Chen Saizhen, Chen Zhongyi, Jin Yinxiu, Tian Ziyou, Lin Xuezheng, Zhu Mengyong, Xu Shanshan, Lin Jiamiao, Xu Lijun
Department of Pharmacy, Taizhou Central Hospital, Taizhou, Zhejiang, China.
Int J Clin Pharmacol Ther. 2013 May;51(5):393-400. doi: 10.5414/CP201828.
The purpose of the present study was to investigate the pharmacokinetics and efficacy of ropivacaine in Chinese patients by intra-articular administration after arthroscopic knee surgery, in order to assess the safety and efficacy.
21 ASA I-II patients received a single-dose of ropivacaine 150 mg in a 20 ml intra-articular injection at the end of surgery. Plasma samples were collected prior to and after ropivacaine administration. Plasma concentrations of ropivacaine were measured by HPLC. Pharmacokinetic parameters were calculated using noncompartmental analysis. Population pharmacokinetic modeling was performed to yield estimates of clearance, volume of distribution, and absorption rate constant. An analysis of covariates on the pharmacokinetic parameters was also carried out. Pain assessments were made using a verbal rating scale at intervals of 2, 4, 8, 12, 24, 36, 48 and 72 hours after surgery.
The results show that the peak plasma concentrations occurred at an average of 0.93 ± 0.56 h (0.25 - 2 h), with a mean of 0.91 ± 0.4 mg/l (range 0.35 - 1.54 mg/l). The peak plasma concentrations and the times to reach the peak plasma concentration exhibited a marked variability among the subjects. All concentrations were well below the estimated toxic threshold (2.2 mg/l). No patient experienced adverse events that may have been related to ropivacaine administration. The intra-articular use of ropivacaine provided excellent control of pain after knee arthroscopy.
Ropivacaine 150 mg provided satisfactory postoperative pain relief and can be safely administered by intraarticular injection in Chinese patients after arthroscopic knee surgery and the pharmacokinetic profiles of ropivacaine exhibited marked variability among the subjects. The high variability of pharmacokinetic profiles in this study may be caused by gender and body weight.
本研究旨在探讨罗哌卡因在膝关节镜手术后经关节腔内给药在中国患者体内的药代动力学及疗效，以评估其安全性和有效性。
21例美国麻醉医师协会（ASA）分级为I-II级的患者在手术结束时接受20ml关节腔内注射单剂量150mg罗哌卡因。在罗哌卡因给药前后采集血浆样本。采用高效液相色谱法测定罗哌卡因的血浆浓度。使用非房室分析计算药代动力学参数。进行群体药代动力学建模以得出清除率、分布容积和吸收速率常数的估计值。还对药代动力学参数的协变量进行了分析。术后2、4、8、12、24、36、48和72小时使用视觉模拟评分法进行疼痛评估。
结果显示，血浆峰浓度平均出现在0.93±0.56小时（0.25 - 2小时），平均值为0.91±0.4mg/l（范围0.35 - 1.54mg/l）。血浆峰浓度及达到血浆峰浓度的时间在受试者之间表现出明显的变异性。所有浓度均远低于估计的中毒阈值（2.2mg/l）。没有患者经历可能与罗哌卡因给药相关的不良事件。关节腔内使用罗哌卡因对膝关节镜检查后的疼痛提供了良好的控制。
150mg罗哌卡因可提供满意的术后疼痛缓解，在中国患者膝关节镜手术后经关节腔内注射可安全给药，且罗哌卡因的药代动力学特征在受试者之间表现出明显的变异性。本研究中药代动力学特征的高变异性可能由性别和体重引起。
