水溶性丙泊酚前药与咪唑安定和芬太尼的催眠协同作用

The hypnotic synergism among a water-soluble prodrug of Propofol,Midazolam and Fentanyl

目的研究水溶性丙泊酚前药(HX0507)与咪唑安定和芬太尼联合使用时对大鼠催眠效应的相互作用。方法将120只SD大鼠随机均分为HX0507(H)组、咪唑安定(M)组、芬太尼(F)组、HX0507+咪唑安定(H+M)组、HX0507+芬太尼(H+F)组、HX0507+咪唑安定+芬太尼(H+M+F)组。通过尾静脉穿刺给药,以翻正反射消失作为终点指标,采用序贯法测定各组大鼠的ED50。用Algebraic法分析HX0507和咪唑安定以及芬太尼的相互作用。结果 H、M组的ED50分别为37.16、25.85mg·kg-1;F组的为28.21μg·kg-1;H+M组中HX0507、咪唑安定的分别为5.67、4.11 mg·kg-1;H+F组中HX0507的为11.87mg·kg-1、芬太尼为9.20μg·kg-1。H+M+F组中,在咪唑安定和芬太尼的剂量分别为1.29 mg·kg-1和1.41μg·kg-1时,HX0507的ED50为6.92 mg·kg-1。结论 HX0507与咪唑安定和/或芬太尼联合应用可产生较强的催眠协同作用,减少HX0507的用量。

OBJECTIVE To determine the hypnotic interaction effects among HX0507,a water-soluble Propofol prodrug,Midazolam and Fentanyl in rats.METHODS A total of 120 adult Sprague-Dawley rats were randomly divided into 6 groups.Rats were intravenously administered with HX0507（H group）,Midazolam（M group）,Fentanyl（F group）,HX0507＋Midazolam（H＋M group）,HX0507＋Fentanyl（H＋F group） and HX0507＋Midazolam＋Fentanyl（H＋M＋F group）,respectively.The up-and-down sequential allocation technique was used to determine the ED50 of each group and the endpoint was defined as loss of righting reflex.The algebraic（fractional） analysis was used to analyze the type of interaction.RESULTS The ED50 of HX0507,Midazolam and Fentanyl were 37.16 mg·kg-1,25.85 mg·kg-1 and 28.21 μg·kg-1,respectively.In H＋M group,the ED50 of HX0507 was 5.67 mg·kg-1 and Midazolam was 4.11 mg·kg-1.In H＋F group,the ED50 of HX0507 was 11.87 mg·kg-1 and Fentanyl was 9.20 μg·kg-1.In H＋M＋F group,when the dose of Midazolam and Fentanyl were 1.29 mg·kg-1 and 1.41 μg·kg-1,respectively.The ED50 of HX0507 was 6.92 mg·kg-1.CONCLUSION The results indicated that HX0507 and Midazolam and/or Fentanyl produced profound hypnotic synergism.