An improved water-soluble prodrug of propofol with high molecular utilization and rapid onset of action.

Affiliation

Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Centre, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China; Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China. Electronic address: [Email]

Abstract

Water-soluble prodrugs of propofol often carry an excess of propofol at the effective dose and have a slower onset of action. Sustained release of the original drug can result in propofol accumulation in the body after administration, causing delays in wakefulness. This situation causes the prodrug to lose the benefits of rapid onset and recovery from the effects of propofol. In the present study, HX0921 (sodium 2-(2-(2,6-diisopropylphenoxy)-2-oxoethoxy)acetate), an improved prodrug of propofol with high utilization of propofol and fast onset of action, was studied. The rate of propofol release from HX0921 was much faster than that from fospropofol (a marketed propofol prodrug) in rat plasma. The 50% effective dose (ED50) of propofol, HX0921 and fospropofol to induce anesthesia in rats was 5.78, 22.19 and 42.44 mg/kg, respectively. After administration at 2 × ED50, the onset time of anesthesia in the HX0921 group was significantly shorter than that in the fospropofol group (0.26 ± 0.15 min vs. 2.24 ± 0.35 min, P < 0.01) and the duration of anesthesia in the HX0921 group was also significantly shorter than that in the fospropofol group (22.35 ± 4.05 min vs. 29.15 ± 5.25 min, P < 0.01). These results suggest that the rapid onset and short action time of HX0921 was due to the rapid release and high molecular utilization of propofol carried by HX0921.

Keywords

High molecular utilization,Propofol,Rapid onset,Short action time,Water-soluble prodrug,

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