硝酸甘油控制性低血压对罗库溴铵的药代动力学和药效动力学影响

Effects of deliberate hypotension induced by nitroglycerin on pharmacokinetics and pharmacodynamics of rocuronium

目的观察硝酸甘油(NTG)控制性低血压(DH)状态下罗库溴铵(肌肉松驰剂)体内效能变化。方法选择全麻下择期鼓室成型术30例,随机分为DH组和对照组。诱导后单次给予罗库溴铵0.6mg·kg-1,用高效液相色谱串联质谱法检测不同时间点罗库溴铵血药浓度。用非线性混合效应模型(NON-MEM)分析罗库溴铵的药代动力学和药效动力学。结果当4个成串反应比值(TOFR)恢复至0.7和0.9时,DH组的罗库溴铵血浆浓度明显低于对照组(P<0.05)。硝酸甘油控制性低血压对其药代动力学影响无显著性差异。药代动力学/药效动力学联合分析显示,对照组罗库溴铵的EC50和γ分别为1.42mg·mL-1,4.32;DH组罗库溴铵的EC50和γ显著降低(分别为1.11mg.L-1,2.92,P<0.05)。结论硝酸甘油控制性低血压能增强罗库溴铵效能,但对其药代动力学无明显影响。

Objective To study the effects of deliberate hypotension（DH）induced by nitroglycerin on the pharmacokinetics and pharmacodynamics（PK/PD）of rocuronium.Methods Thirty patients scheduled for elective tympanoplasty were randomly assigned to DH group or control group（n=15 for the each）.After induction without any relaxant,every patient received a single dose of rocuronium（0.6 mg·kg-1）via peripheral vein.Serial arterial blood samples were taken to determine the plasma concentration of rocuronium by HPLC-MS/MS.The PK/PD analysis was performed with NONMEM.Results During the recovery stage（TOFR=0.7,0.9）,the plasma concentration of DH group decreased significantly compared to those of control group（P0.05）.PK/PD linked model analysis indicated that deliberate hypotension induced by nitroglycerin had no significant effect on the pharmacokinetic parameters.EC50 and γ in the DH group decreased significantly（1.11 mg·L-1 vs 1.42 mg·L-1;2.92 vs 4.32,respectively）compared to those of control group.Conclusion Deliberate hypotension induced by nitroglycerin could augment the potency of rocuronium,but it made no difference in the pharmacokinetic parameters.