[The sedative-hypnotic effects and safety of oral administrated propofol prodrugs hx0969w and fospropofol disodiun in comparison with propofol emulsion in rats].

ABSTRACT

OBJECTIVE: To estimate the median effective dose (EDs0) of oral administrated HX0969w, fospropofol disodium and propofol emulsion in rats, and to compare the sedative-hypnotic effects and safety of the three drugs. METHODS: The ED50 of the three drugs were determined using sequential method. Thirty healthy adult Sprague-Dawley rats were divided into three groups randomly, being orally administered with HX0969w (n=10), fospropofol disodium (n=10) and propofol emulsion (n=10), respectively. The neurobehavioral performance of the rats was observed. The time of loss of forepaw righting reflex (LRR) and the time of recovery of forepaw righting reflex (RRR) were recorded. RESULTS: The ED50 of oral HX0969w, fospropofol disodium and propofol emulsion were 96.5 mg/kg, 130.0 mg/kg and 113.8 mg/kg, respectively. HX0969w, fospropofol disodium and propofol emulsion had a mean LRR of (10.0 +/- 2.9) min,(7.5 +/- 2.8) min and (16.0 +/- 5.9) min; respectively; and a mean RRR of (66.9 +/- 21.5) min, (131.9 +/- 32.7) min and (198.9 +/- 110.0) min, respectively. CONCLUSION: HX0969w, fospropofol disodium and propofol emulsion can produce sedative-hypnotic effects and they are safe when administered by oral route. The two propofol prodrugs HX0969w and fospropofol disodium have shorter LRR than propofol emulsion. HX0969w also has a shorter RRR than fospropofol disodium and propofol emulsion.