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Pharmacokinetics and Safety of Esketamine in Chinese Patients Undergoing Painless Gastroscopy in Comparison with Ketamine: A Randomized, Open-Label Clinical Study

PURPOSE: 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. PATIENTS AND METHODS: A randomized,...

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Autores principales: Wang, Jing, Huang, Jie, Yang, Shuang, Cui, Chang, Ye, Ling, Wang, Sai-ying, Yang, Guo-ping, Pei, Qi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902860/
https://www.ncbi.nlm.nih.gov/pubmed/31827320
http://dx.doi.org/10.2147/DDDT.S224553
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author Wang, Jing
Huang, Jie
Yang, Shuang
Cui, Chang
Ye, Ling
Wang, Sai-ying
Yang, Guo-ping
Pei, Qi
author_facet Wang, Jing
Huang, Jie
Yang, Shuang
Cui, Chang
Ye, Ling
Wang, Sai-ying
Yang, Guo-ping
Pei, Qi
author_sort Wang, Jing
collection PubMed
description PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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, P<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. CONCLUSION: 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.
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spelling pubmed-69028602019-12-11 Pharmacokinetics and Safety of Esketamine in Chinese Patients Undergoing Painless Gastroscopy in Comparison with Ketamine: A Randomized, Open-Label Clinical Study Wang, Jing Huang, Jie Yang, Shuang Cui, Chang Ye, Ling Wang, Sai-ying Yang, Guo-ping Pei, Qi Drug Des Devel Ther Original Research PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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, P<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. CONCLUSION: 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. Dove 2019-12-06 /pmc/articles/PMC6902860/ /pubmed/31827320 http://dx.doi.org/10.2147/DDDT.S224553 Text en © 2019 Wang et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Wang, Jing
Huang, Jie
Yang, Shuang
Cui, Chang
Ye, Ling
Wang, Sai-ying
Yang, Guo-ping
Pei, Qi
Pharmacokinetics and Safety of Esketamine in Chinese Patients Undergoing Painless Gastroscopy in Comparison with Ketamine: A Randomized, Open-Label Clinical Study
title Pharmacokinetics and Safety of Esketamine in Chinese Patients Undergoing Painless Gastroscopy in Comparison with Ketamine: A Randomized, Open-Label Clinical Study
title_full Pharmacokinetics and Safety of Esketamine in Chinese Patients Undergoing Painless Gastroscopy in Comparison with Ketamine: A Randomized, Open-Label Clinical Study
title_fullStr Pharmacokinetics and Safety of Esketamine in Chinese Patients Undergoing Painless Gastroscopy in Comparison with Ketamine: A Randomized, Open-Label Clinical Study
title_full_unstemmed Pharmacokinetics and Safety of Esketamine in Chinese Patients Undergoing Painless Gastroscopy in Comparison with Ketamine: A Randomized, Open-Label Clinical Study
title_short Pharmacokinetics and Safety of Esketamine in Chinese Patients Undergoing Painless Gastroscopy in Comparison with Ketamine: A Randomized, Open-Label Clinical Study
title_sort pharmacokinetics and safety of esketamine in chinese patients undergoing painless gastroscopy in comparison with ketamine: a randomized, open-label clinical study
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902860/
https://www.ncbi.nlm.nih.gov/pubmed/31827320
http://dx.doi.org/10.2147/DDDT.S224553
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