Ciprofol Explained

Watchedfields:changed
Drug Name:Ciprofol
Inn:Cipepofol
Metabolism:Liver glucuronidation
Excretion:Kidney
Cas Number:1637741-58-2
Pubchem:86301664
Chemspiderid:76794458
Unii:M3WGS532VY
Synonyms:(R)-2-(1-cyclopropylethyl)-6-isopropylphenol
Iupac Name:2-[(1''R'')-1-cyclopropylethyl]-6-isopropylphenol
C:14
H:20
O:1
Smiles:CC(C1=CC=CC([C@@H](C2CC2)C)=C1O)C
Stdinchi:1S/C14H20O/c1-9(2)12-5-4-6-13(14(12)15)10(3)11-7-8-11/h4-6,9-11,15H,7-8H2,1-3H3/t10-/m1/s1
Stdinchikey:BMEARIQHWSVDBS-SNVBAGLBSA-N

Ciprofol (also known as cipepofol, or HSK3486)[1] is a novel 2,6-disubstituted phenol derivative that is used for the intravenous induction of general anesthesia.[2] [3] A short-acting and highly selective γ-aminobutyric acid agonist,[4] ciprofol is 4–6 times more potent than other phenol derivatives such as propofol or fospropofol.[5]

As of 2023, it is still an investigational drug.[6] Manufactured by Haisco Pharmaceutical Group of Chengdu, Sichuan, China, ciprofol has undergone phase I and II trials in Australia and China.[6] [7] [8] In these early studies, ciprofol appears to be comparable in efficacy to propofol and is associated with fewer adverse events.[3] [5] [9] [10] [11] [12] [13] [14] [15] [16]

Physical properties

Ciprofol is an optically active 2,6-disubstituted alkylphenol with a cyclopropylethyl group incorporated at the second carbon atom. This cyclopropyl group increases the steric effects and introduces stereoselective effects over its anesthetic properties. These properties appear to increase the anesthetic potency of ciprofol, when compared with propofol.[7]

Medical use

Ciprofol is used for the intravenous induction of general anesthesia.[2] [3] As of 2023, it is still an investigational drug. Thus far, it has been found to be efficacious as a general anesthetic in patients undergoing gynecological surgery[5] [9] and kidney transplantation,[17] as well as for endoscopic procedures such as bronchoscopy,[13] [18] esophagogastroduodenoscopy and colonoscopy.[19] [20]

Ciprofol has also been used for sedation of critically ill patients undergoing mechanical ventilation in the intensive care unit,[21] as well as for the treatment of agitation and delirium in that patient population.[22] When combined with mild therapeutic hypothermia, ciprofol may also be useful as a cerebral protective agent in the setting of cerebral ischemia-reperfusion injury.[23]

Experimental use

In experimental models of isoproterenol-induced myocardial infarction (using mice as subjects), ciprofol appears to protect the heart against oxidative damage, inflammation and apoptosis of cardiac muscle cells.[24]

Side effects

When compared with propofol, side effects such as pain on injection[13] and respiratory depression appear to be less common with ciprofol.[14]

Pharmacology

Pharmacokinetics

Compared to propofol, ciprofol exhibits stronger binding to the GABAA receptor and elicits a greater enhancement of GABAA receptor-mediated neurotransmission.[25]

It is not necessary to adjust the dose in people with mild or moderate renal impairment,[26] or in those with mild or moderate hepatic impairment.[27] In elderly people, a slightly lower dose (0.3 mg/kg) appears to be similar in efficacy to the higher doses administered to younger people but is associated with fewer adverse effects.[28] [29]

Pharmacodynamics

Ciprofol exhibits pharmacodynamic properties similar to those of propofol, including both rapid onset and rapid offset. Ciprofol appears to have similar effects upon the respiratory and cardiovascular systems as those propofol.[5] At doses of 0.4 mg/kg to 0.5 mg/kg, ciprofol induces equivalent sedation/anesthesia and has an incidence of adverse events similar to that of propofol 2.0 mg/kg.[15] [16]

Biodegradation and toxicity

Ciprofol is characterized by a rapid onset of action, and predictable absorption, distribution, metabolism, excretion processes. The compound undergoes glucuronidation in the liver, followed by excretion by the kidneys.[30]

Further reading

Notes and References

  1. Web site: . Cipepofol (Synonyms: Ciprofol; HSK3486). MedChemExpress. MedChemExpress LLC. Monmouth Junction, New Jersey. 2023. 11 May 2023.
  2. Wang X, Wang X, Liu J, Zuo YX, Zhu QM, Wei XC, Zou XH, Luo AL, Zhang FX, Li YL, Zheng H, Li H, Wang S, Wang DX, Guo QL, Liu CM, Wang YT, Zhu ZQ, Wang GY, Ai YQ, Xu MJ . 6 . Effects of ciprofol for the induction of general anesthesia in patients scheduled for elective surgery compared to propofol: a phase 3, multicenter, randomized, double-blind, comparative study . European Review for Medical and Pharmacological Sciences . 26 . 5 . 1607–1617 . March 2022 . 35302207 .
  3. Zeng Y, Wang DX, Lin ZM, Liu J, Wei XC, Deng J, Liu YF, Ma EL, Yang MC, Zheng H, Yu XD, Guo QL, Guan YJ . 6 . Efficacy and safety of HSK3486 for the induction and maintenance of general anesthesia in elective surgical patients: a multicenter, randomized, open-label, propofol-controlled phase 2 clinical trial . European Review for Medical and Pharmacological Sciences . 26 . 4 . 1114–1124 . February 2022 . 35253166 .
  4. Liao J, Li M, Huang C, Yu Y, Chen Y, Gan J, Xiao J, Xiang G, Ding X, Jiang R, Li P, Yang M . 6 . Pharmacodynamics and Pharmacokinetics of HSK3486, a Novel 2,6-Disubstituted Phenol Derivative as a General Anesthetic . Frontiers in Pharmacology . 13 . 830791 . 2022 . 35185584 . 8851058 . 10.3389/fphar.2022.830791 . free .
  5. Chen BZ, Yin XY, Jiang LH, Liu JH, Shi YY, Yuan BY . The efficacy and safety of ciprofol use for the induction of general anesthesia in patients undergoing gynecological surgery: a prospective randomized controlled study . BMC Anesthesiology . 22 . 1 . 245 . August 2022 . 35922771 . 9347095 . 10.1186/s12871-022-01782-7 . free .
  6. Lu M, Liu J, Wu X, Zhang Z . Ciprofol: A Novel Alternative to Propofol in Clinical Intravenous Anesthesia? . BioMed Research International . 2023 . 7443226 . 2023 . 36714027 . 9879693 . 10.1155/2023/7443226 . free .
  7. Qin L, Ren L, Wan S, Liu G, Luo X, Liu Z, Li F, Yu Y, Liu J, Wei Y . 6 . Design, Synthesis, and Evaluation of Novel 2,6-Disubstituted Phenol Derivatives as General Anesthetics . Journal of Medicinal Chemistry . 60 . 9 . 3606–3617 . May 2017 . 28430430 . 10.1021/acs.jmedchem.7b00254 .
  8. Nair A, Seelam S . Ciprofol- a game changing intravenous anesthetic or another experimental drug! . Saudi Journal of Anaesthesia . 16 . 2 . 258–259 . 2022 . 35431734 . 9009555 . 10.4103/sja.sja_898_21 . free .
  9. Man Y, Xiao H, Zhu T, Ji F . Study on the effectiveness and safety of ciprofol in anesthesia in gynecological day surgery: a randomized double-blind controlled study . BMC Anesthesiology . 23 . 1 . 92 . March 2023 . 36964501 . 10039513 . 10.1186/s12871-023-02051-x . free .
  10. Chen X, Guo P, Yang L, Liu Z, Yu D . Comparison and Clinical Value of Ciprofol and Propofol in Intraoperative Adverse Reactions, Operation, Resuscitation, and Satisfaction of Patients under Painless Gastroenteroscopy Anesthesia . Contrast Media & Molecular Imaging . 2022 . 9541060 . 2022 . 35935320 . 9314164 . 10.1155/2022/9541060 . free .
  11. Zhong J, Zhang J, Fan Y, Zhu M, Zhao X, Zuo Z, Zhou X, Miao C . 6 . Efficacy and safety of Ciprofol for procedural sedation and anesthesia in non-operating room settings . Journal of Clinical Anesthesia . 85 . 111047 . May 2023 . 36599219 . 10.1016/j.jclinane.2022.111047 . 255468218 . free .
  12. Liang P, Dai M, Wang X, Wang D, Yang M, Lin X, Zou X, Jiang K, Li Y, Wang L, Shangguan W, Ren J, He H . 6 . Efficacy and safety of ciprofol vs. propofol for the induction and maintenance of general anaesthesia: A multicentre, single-blind, randomised, parallel-group, phase 3 clinical trial . European Journal of Anaesthesiology . 40 . 6 . 399–406 . June 2023 . 36647565 . 10155686 . 10.1097/EJA.0000000000001799 .
  13. Luo Z, Tu H, Zhang X, Wang X, Ouyang W, Wei X, Zou X, Zhu Z, Li Y, Shangguan W, Wu H, Wang Y, Guo Q . 6 . Efficacy and Safety of HSK3486 for Anesthesia/Sedation in Patients Undergoing Fiberoptic Bronchoscopy: A Multicenter, Double-Blind, Propofol-Controlled, Randomized, Phase 3 Study . CNS Drugs . 36 . 3 . 301–313 . March 2022 . 35157236 . 8927014 . 10.1007/s40263-021-00890-1 .
  14. Hu C, Ou X, Teng Y, Shu S, Wang Y, Zhu X, Kang Y, Miao J . 6 . Sedation Effects Produced by a Ciprofol Initial Infusion or Bolus Dose Followed by Continuous Maintenance Infusion in Healthy Subjects: A Phase 1 Trial . Advances in Therapy . 38 . 11 . 5484–5500 . November 2021 . 34559359 . 8523013 . 10.1007/s12325-021-01914-4 .
  15. Teng Y, Ou M, Wang X, Zhang W, Liu X, Liang Y, Li K, Wang Y, Ouyang W, Weng H, Li J, Yao S, Meng J, Shangguan W, Zuo Y, Zhu T, Liu B, Liu J . 6 . Efficacy and safety of ciprofol for the sedation/anesthesia in patients undergoing colonoscopy: Phase IIa and IIb multi-center clinical trials . European Journal of Pharmaceutical Sciences . 164 . 105904 . September 2021 . 34116176 . 10.1016/j.ejps.2021.105904 . free .
  16. Zhu Q, Luo Z, Wang X, Wang D, Li J, Wei X, Tang J, Yao S, Ouyang W, Zhang W, Zuo Y, Wang X, Liu J . 6 . Efficacy and safety of ciprofol versus propofol for the induction of anesthesia in adult patients: a multicenter phase 2a clinical trial . International Journal of Clinical Pharmacy . 45 . 2 . 473–482 . April 2023 . 36680620 . 10147789 . 10.1007/s11096-022-01529-x .
  17. Qin K, Qin WY, Ming SP, Ma XF, Du XK . Effect of ciprofol on induction and maintenance of general anesthesia in patients undergoing kidney transplantation . European Review for Medical and Pharmacological Sciences . 26 . 14 . 5063–5071 . July 2022 . 35916802 .
  18. Wu B, Zhu W, Wang Q, Ren C, Wang L, Xie G . Efficacy and safety of ciprofol-remifentanil versus propofol-remifentanil during fiberoptic bronchoscopy: A prospective, randomized, double-blind, non-inferiority trial . Frontiers in Pharmacology . 13 . 1091579 . 2022 . 36618929 . 9812563 . 10.3389/fphar.2022.1091579 . free .
  19. Li J, Wang X, Liu J, Wang X, Li X, Wang Y, Ouyang W, Li J, Yao S, Zhu Z, Guo Q, Yu Y, Meng J, Zuo Y . 6 . Comparison of ciprofol (HSK3486) versus propofol for the induction of deep sedation during gastroscopy and colonoscopy procedures: A multi-centre, non-inferiority, randomized, controlled phase 3 clinical trial . Basic & Clinical Pharmacology & Toxicology . 131 . 2 . 138–148 . August 2022 . 35653554 . 9543620 . 10.1111/bcpt.13761 .
  20. Long YQ, Feng CD, Ding YY, Feng XM, Liu H, Ji FH, Peng K . Esketamine as an Adjuvant to Ciprofol or Propofol Sedation for Same-Day Bidirectional Endoscopy: Protocol for a Randomized, Double-Blind, Controlled Trial With Factorial Design . Frontiers in Pharmacology . 13 . 821691 . 2022 . 35370640 . 8975265 . 10.3389/fphar.2022.821691 . free .
  21. Liu Y, Yu X, Zhu D, Zeng J, Lin Q, Zang B, Chen C, Liu N, Liu X, Gao W, Guan X . 6 . Safety and efficacy of ciprofol vs. propofol for sedation in intensive care unit patients with mechanical ventilation: a multi-center, open label, randomized, phase 2 trial . Chinese Medical Journal . 135 . 9 . 1043–1051 . May 2022 . 34924506 . 9276409 . 10.1097/CM9.0000000000001912 .
  22. Liu GL, Wu GZ, Ge D, Zhou HJ, Cui S, Gao K, Sun WJ, Yu DH, Liu SB, Liu JJ . 6 . Efficacy and safety of ciprofol for agitation and delirium in the ICU: A multicenter, single-blind, 3-arm parallel randomized controlled trial study protocol . Frontiers in Medicine . 9 . 1024762 . 2023 . 36698817 . 9868613 . 10.3389/fmed.2022.1024762 . free .
  23. Wang YC, Wu MJ, Zhou SL, Li ZH . Protective effects of combined treatment with ciprofol and mild therapeutic hypothermia during cerebral ischemia-reperfusion injury . World Journal of Clinical Cases . 11 . 3 . 487–492 . January 2023 . 36793629 . 9923870 . 10.12998/wjcc.v11.i3.487 . free .
  24. Yang Y, Xia Z, Xu C, Zhai C, Yu X, Li S . Ciprofol attenuates the isoproterenol-induced oxidative damage, inflammatory response and cardiomyocyte apoptosis . Frontiers in Pharmacology . 13 . 1037151 . 2022 . 36483733 . 9723392 . 10.3389/fphar.2022.1037151 . free .
  25. Duan G, Lan H, Shan W, Wu Y, Xu Q, Dong X, Mei P, You M, Jin L, Wu J . 6 . Clinical effect of different doses of ciprofol for induction of general anesthesia in elderly patients: A randomized, controlled trial . Pharmacology Research & Perspectives . 11 . 2 . e01066 . April 2023 . 36811327 . 9944862 . 10.1002/prp2.1066 . 257098376 .
  26. Liu SB, Yao X, Tao J, Yang JJ, Zhao YY, Liu DW, Wang SY, Sun SK, Wang X, Yan PK, Wu N, Liu X, Zhang XJ, Tian X, Liu ZS . 6 . Population total and unbound pharmacokinetics and pharmacodynamics of ciprofol and M4 in subjects with various renal functions . British Journal of Clinical Pharmacology . 89 . 3 . 1139–1151 . March 2023 . 36217805 . 10.1111/bcp.15561 . 252818288 .
  27. Hu Y, Li X, Liu J, Chen H, Zheng W, Zhang H, Wu M, Li C, Zhu X, Lou J, Yan P, Wu N, Liu X, Ma S, Wang X, Ding Y, Xuan C . 6 . Safety, pharmacokinetics and pharmacodynamics of a novel γ-aminobutyric acid (GABA) receptor potentiator, HSK3486, in Chinese patients with hepatic impairment . Annals of Medicine . 54 . 1 . 2769–2780 . December 2022 . 36217101 . 9559057 . 10.1080/07853890.2022.2129433 .
  28. Li X, Yang D, Li Q, Wang H, Wang M, Yan P, Wu N, Li F, Ma S, Ding Y, Liu J, Wang H . 6 . Safety, Pharmacokinetics, and Pharmacodynamics of a Single Bolus of the γ-aminobutyric Acid (GABA) Receptor Potentiator HSK3486 in Healthy Chinese Elderly and Non-elderly . Frontiers in Pharmacology . 12 . 735700 . 2021 . 34512361 . 8430033 . 10.3389/fphar.2021.735700 . free .
  29. Ding YY, Long YQ, Yang HT, Zhuang K, Ji FH, Peng K . Efficacy and safety of ciprofol for general anaesthesia induction in elderly patients undergoing major noncardiac surgery: A randomised controlled pilot trial . European Journal of Anaesthesiology . 39 . 12 . 960–963 . December 2022 . 36214498 . 10.1097/EJA.0000000000001759 . 252779399 .
  30. Bian Y, Zhang H, Ma S, Jiao Y, Yan P, Liu X, Ma S, Xiong Y, Gu Z, Yu Z, Huang C, Miao L . 6 . Mass balance, pharmacokinetics and pharmacodynamics of intravenous HSK3486, a novel anaesthetic, administered to healthy subjects . British Journal of Clinical Pharmacology . 87 . 1 . 93–105 . January 2021 . 32415708 . 10.1111/bcp.14363 . 218658207 . free .

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