Ciprofol

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

As of 2023, it is still an investigational drug. Manufactured by Haisco Pharmaceutical Group of Chengdu, Sichuan, China, ciprofol has undergone phase I and II trials in Australia and China. In these early studies, ciprofol appears to be comparable in efficacy to propofol and is associated with fewer adverse events.

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.

Medical use
Ciprofol is used for the intravenous induction of general anesthesia. 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 and kidney transplantation, as well as for endoscopic procedures such as bronchoscopy, esophagogastroduodenoscopy and colonoscopy.

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

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.

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

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

It is not necessary to adjust the dose in people with mild or moderate renal impairment, or in those with mild or moderate hepatic impairment. 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.

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. 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.

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.