The Sedative-hypnotic Effects and Safety of Oral Administrated Propofol Prodrugs HX0969w and Fospropofol Disodium in Comparison with Propofol Emulsion in Rats
目的 采用序贯法测定大鼠口服（灌胃）HX0969w、磷丙泊酚钠（fospropofol disodium）和丙泊酚乳剂后产生镇静催眠效应的半数有效量（ED\50），并观察3种药物等效剂量（2ED\50）灌胃大鼠后的镇静催眠作用及安全性。方法 采用序贯实验法确定各药物最小剂量和最大剂量后，根据ED\50计算公式计算3种药物的ED\50。选择30只健康SD成年大鼠，随机分为3组：HX0969w组（\n=10）、磷丙泊酚钠组（\n=10）和丙泊酚乳剂组（\n=10）。大鼠灌胃给药后立即观察大鼠的神经行为学表现，并记录镇静催眠起效时间和恢复时间。结果 HX0969w、磷丙泊酚钠和丙泊酚乳剂的ED\50分别为96.5 mg/kg、130.0 mg/kg和113.8 mg/kg。灌胃等效剂量（2ED\50）的HX0969w、磷丙泊酚钠和丙泊酚乳剂后，大鼠翻正反射消失的平均时间分别是：（10.0±2.9） min、（7.5±2.8） min 和 （16.0±5.9） min；恢复时间的平均值分别为（66.9±21.5） min、（131.9±32.7） min 和（198.9±110.0） min。结论 3种药物灌胃后均可产生镇静催眠作用且安全。两种丙泊酚前药（HX0969w和磷丙泊酚钠）灌胃后的镇静催眠起效时间均快于丙泊酚乳剂，且HX0969w翻正反射恢复最快。
英文摘要:
Objective To estimate the median effective dose (ED\50) 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 ED\50 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 ED\50 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.
