Wang Jing, Huang Jie, Yang Shuang, Cui Chang, Ye Ling, Wang Sai-Ying, Yang Guo-Ping, Pei Qi
Center for Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People's Republic of China.
Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People's Republic of China.
Drug Des Devel Ther. 2019 Dec 6;13:4135-4144. doi: 10.2147/DDDT.S224553. eCollection 2019.
To assess the pharmacokinetics and safety of pure S-ketamine (esketamine) in Chinese patients undergoing painless gastroscopy and evaluate the potential advantage of esketamine in clinical treatment compared with racemate ketamine hydrochloride injection.
A randomized, open-label, parallel-controlled, Phase I study was performed with 32 patients undergoing painless gastroscopy. Patients received a single dose of esketamine (0.5 mg/kg) or racemic ketamine (1 mg/kg, esketamine:R-ketamine=1:1), injected in 10 s. Blood samples were collected for pharmacokinetic analysis. The concentrations of esketamine, R-ketamine, S-norketamine, and R-norketamine were measured with a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method.
After administering a single dose of esketamine and racemate ketamine, the pharmacokinetics parameters of esketamine and S-norketamine are both similar in treatment groups. The clearance of esketamine in two groups was 18.1±3.2 and 18.4±3.4 mL/min•kg, respectively. However, in the ketamine group, esketamine has a larger clearance than R-ketamine (18.4±3.4 mL/min·kg vs 15.8±3.1 mL/min·kg, <0.001). Further analysis showed that gender did not affect the pharmacokinetics of esketamine and racemate ketamine. Regarding the safety of esketamine and racemate ketamine, no serious adverse events were observed during treatment, and the incidences of adverse events were 75.0% (esketamine) and 87.5% (racemate ketamine). The main adverse reactions were dizziness, agitation, nausea, vomiting, headache, and fatigue. However, compared with racemic ketamine, esketamine offers a shorter recovery time (9 mins vs. 13 mins, P<0.05) and orientation recovery time (11.5 mins vs. 17 mins, P<0.05) after short anesthesia.
Esketamine administration as a single dose of 0.5 mg/kg was generally safe and tolerated in patients undergoing painless gastroscopy. In terms of anesthesia, a relatively small dose of esketamine can be used instead of racemate ketamine for routine treatment without consideration of gender differences.
评估纯S-氯胺酮（艾司氯胺酮）在中国接受无痛胃镜检查患者中的药代动力学及安全性，并评估与消旋氯胺酮盐酸盐注射液相比，艾司氯胺酮在临床治疗中的潜在优势。
对32例接受无痛胃镜检查的患者进行了一项随机、开放标签、平行对照的I期研究。患者接受单剂量艾司氯胺酮（0.5mg/kg）或消旋氯胺酮（1mg/kg，艾司氯胺酮：R-氯胺酮=1:1），于10秒内注射完毕。采集血样进行药代动力学分析。采用经过验证的液相色谱-串联质谱（LC-MS/MS）法测定艾司氯胺酮、R-氯胺酮、S-去甲氯胺酮和R-去甲氯胺酮的浓度。
单剂量给予艾司氯胺酮和消旋氯胺酮后，各治疗组中艾司氯胺酮和S-去甲氯胺酮的药代动力学参数相似。两组中艾司氯胺酮的清除率分别为18.1±3.2和18.4±3.4 mL/min•kg。然而，在氯胺酮组中，艾司氯胺酮的清除率高于R-氯胺酮（18.4±3.4 mL/min·kg对15.8±3.1 mL/min·kg，<0.001）。进一步分析表明，性别不影响艾司氯胺酮和消旋氯胺酮的药代动力学。关于艾司氯胺酮和消旋氯胺酮的安全性，治疗期间未观察到严重不良事件，不良事件发生率分别为75.0%（艾司氯胺酮）和87.5%（消旋氯胺酮）。主要不良反应为头晕、激动、恶心、呕吐、头痛和疲劳。然而，与消旋氯胺酮相比，艾司氯胺酮在短暂麻醉后的恢复时间（9分钟对13分钟，P<0.05）和定向恢复时间（11.5分钟对17分钟，P<0.05）更短。
单剂量0.5mg/kg的艾司氯胺酮给药在接受无痛胃镜检查的患者中总体安全且耐受性良好。在麻醉方面，可使用相对小剂量的艾司氯胺酮替代消旋氯胺酮进行常规治疗，无需考虑性别差异。
