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

Overview

Journal Drug Des Devel Ther

Specialty Pharmacology

Date 2019 Dec 13

PMID 31827320

Citations 81

Authors

Jing Wang

Jie Huang

Shuang Yang

Chang Cui

Ling Ye

Sai-Ying Wang

Guo-Ping Yang

Qi Pei

Affiliations

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Abstract

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, <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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References

Mion G, Villevieille T . Ketamine pharmacology: an update (pharmacodynamics and molecular aspects, recent findings). CNS Neurosci Ther. 2013; 19(6):370-80. PMC: 6493357. DOI: 10.1111/cns.12099. View

Ihmsen H, Geisslinger G, Schuttler J . Stereoselective pharmacokinetics of ketamine: R(-)-ketamine inhibits the elimination of S(+)-ketamine. Clin Pharmacol Ther. 2001; 70(5):431-8. DOI: 10.1067/mcp.2001.119722. View

Kapur J . Role of NMDA receptors in the pathophysiology and treatment of status epilepticus. Epilepsia Open. 2018; 3(Suppl Suppl 2):165-168. PMC: 6293062. DOI: 10.1002/epi4.12270. View

Frey T, Florin T, Caruso M, Zhang N, Zhang Y, Mittiga M . Effect of Intranasal Ketamine vs Fentanyl on Pain Reduction for Extremity Injuries in Children: The PRIME Randomized Clinical Trial. JAMA Pediatr. 2018; 173(2):140-146. PMC: 6439599. DOI: 10.1001/jamapediatrics.2018.4582. View

Sinner B, Graf B . Ketamine. Handb Exp Pharmacol. 2008; (182):313-33. DOI: 10.1007/978-3-540-74806-9_15. View

Salloum N, Fava M, Freeman M, Flynn M, Hoeppner B, Hock R . Efficacy of intravenous ketamine treatment in anxious versus nonanxious unipolar treatment-resistant depression. Depress Anxiety. 2019; 36(3):235-243. DOI: 10.1002/da.22875. View

Domino E . Taming the ketamine tiger. 1965. Anesthesiology. 2010; 113(3):678-84. DOI: 10.1097/ALN.0b013e3181ed09a2. View

Pfenninger E, Durieux M, Himmelseher S . Cognitive impairment after small-dose ketamine isomers in comparison to equianalgesic racemic ketamine in human volunteers. Anesthesiology. 2002; 96(2):357-66. DOI: 10.1097/00000542-200202000-00022. View

Laskowski K, Stirling A, McKay W, Lim H . A systematic review of intravenous ketamine for postoperative analgesia. Can J Anaesth. 2011; 58(10):911-23. DOI: 10.1007/s12630-011-9560-0. View

10.

Peltoniemi M, Hagelberg N, Olkkola K, Saari T . Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthesia and Pain Therapy. Clin Pharmacokinet. 2016; 55(9):1059-77. DOI: 10.1007/s40262-016-0383-6. View

11.

Adams H, Werner C . [From the racemate to the eutomer: (S)-ketamine. Renaissance of a substance?]. Anaesthesist. 1998; 46(12):1026-42. DOI: 10.1007/s001010050503. View

12.

Himmelseher S, Pfenninger E . [The clinical use of S-(+)-ketamine--a determination of its place]. Anasthesiol Intensivmed Notfallmed Schmerzther. 1999; 33(12):764-70. DOI: 10.1055/s-2007-994851. View

13.

Zou L, Tian S, Quan X, Ye T . [Psychedelic effects of subanesthetic doses of ketamine]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2009; 31(1):68-72. View

14.

Zanos P, Moaddel R, Morris P, Riggs L, Highland J, Georgiou P . Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms. Pharmacol Rev. 2018; 70(3):621-660. PMC: 6020109. DOI: 10.1124/pr.117.015198. View

15.

Domino E, CHODOFF P, CORSSEN G . PHARMACOLOGIC EFFECTS OF CI-581, A NEW DISSOCIATIVE ANESTHETIC, IN MAN. Clin Pharmacol Ther. 1965; 6:279-91. DOI: 10.1002/cpt196563279. View

16.

Bell R, Dahl J, Moore R, Kalso E . Peri-operative ketamine for acute post-operative pain: a quantitative and qualitative systematic review (Cochrane review). Acta Anaesthesiol Scand. 2005; 49(10):1405-28. DOI: 10.1111/j.1399-6576.2005.00814.x. View

17.

White P, Schuttler J, Shafer A, Stanski D, Horai Y, TREVOR A . Comparative pharmacology of the ketamine isomers. Studies in volunteers. Br J Anaesth. 1985; 57(2):197-203. DOI: 10.1093/bja/57.2.197. View

18.

Sigtermans M, Dahan A, Mooren R, Bauer M, Kest B, Sarton E . S(+)-ketamine effect on experimental pain and cardiac output: a population pharmacokinetic-pharmacodynamic modeling study in healthy volunteers. Anesthesiology. 2009; 111(4):892-903. DOI: 10.1097/ALN.0b013e3181b437b1. View

19.

Engelhardt W, Stahl K, Marouche A, Hartung E . [Recovery time after (S)-ketamine or ketamine racemate. Recovery time after short anesthesia in volunteers]. Anaesthesist. 1998; 47(3):184-92. DOI: 10.1007/s001010050546. View

20.

Geisslinger G, Hering W, Thomann P, Knoll R, Kamp H, Brune K . Pharmacokinetics and pharmacodynamics of ketamine enantiomers in surgical patients using a stereoselective analytical method. Br J Anaesth. 1993; 70(6):666-71. DOI: 10.1093/bja/70.6.666. View