Novel propofol derivatives and implications for anesthesia practice

Abstract

Propofol (2,6-diisopropylphenol) is the most commonly used intravenous agent for induction of anesthesia. It is also used for maintenance of anesthesia and sedation in both Intensive Care Units and outpatient procedural settings. Its success in the clinical setting has been a result of its rapid onset, short duration of action, and minimal side effects despite disadvantages associated with its oil emulsion formulation. Early attempts to alter the standard emulsion or to develop new formulations with cyclodextrins and micelles to resolve issues with pain upon injection, the need for antimicrobial agents, and possible hyperlipidemia have mostly failed. With these challenges in the foreground, attention has now shifted to the use of more prodrugs and exogenous alternatives, the success of which is yet to be determined. These new agents must offer significant clinical advantages over the well-entrenched, generic propofol oil emulsion to justify higher costs and to be well received in the increasingly cost-conscious healthcare marketplace.

Clinical efficacy of intravenous anesthesia on breast segmental surgery and its effects on oxidative stress response and hemodynamics of patients

“…In clinical general anesthesia, propofol combined with remifentanil is mainly used for drug compatibility, which has the advantages of rapid anesthesia and postoperative recovery ( 15 , 16 ). Propofol ( 17 ) can be rapidly removed from the central ventricle through liver metabolism and renal excretion, while remifentanil ( 18 , 19 ) can be rapidly degraded by non-specific esterase, which was advantageous in rapid action, short action time, rapid removal without accumulation during continuous infusion. Inhalation anesthesia also has advantages including quick effect and discharge, little influence on circulation and respiration, and non-invasive administration.…”

Allosteric GABAA Receptor Modulators—A Review on the Most Recent Heterocyclic Chemotypes and Their Synthetic Accessibility

“…Propofol is a hydrophobic compound for intravenous application in a lipid-solution. It was first approved for use in the 1980s and has quickly advanced to become the most frequently administered intravenous drug for the induction of general anesthesia and a common choice for the maintenance of general anesthesia as well as procedural sedation [37]. Rapid inductions, rapid terminal half-life time, low incidence of postoperative nausea and vomiting, as well as rapid psychomotor recovery make it a very versatile hypnotic drug [38].…”

The preclinical pharmacological study on HX0969W, a novel water-soluble pro-drug of propofol, in rats

“…However, many serious side effects have been related to its lipid emulsion formations, such as emulsion instability, injection pain, hyperlipidemia, infection, fat metabolism disorder, and propofol-related infusion syndrome (Diaz et al, 2014;Lee et al, 2014;Mirrakhimov et al, 2015;Pestana, Garcia-de Lorenzo & Madero, 1996;Prankerd & Stella, 1990;Singh, Jindal & Singh, 2011;Wachowski et al, 1999;Wolf et al, 2001;Zhou et al, 2015). The pro-drug design approach was widely used to develop the novel water-soluble propofol, which could effectively avoid the limitations associated with its lipid emulsion formulation (Feng et al, 2017).…”