甲磺酸罗哌卡因和盐酸罗哌卡因硬膜外阻滞的药代动力学特征比较

Comparision of pharmacokinetics between ropivacaine methanesulfonate and ropivacaine hydrochloride during epidural block

目的比较0.894%甲磺酸罗哌卡因和0.75%盐酸罗哌卡因的药代动力学特征。方法 40例择期下腹部、下肢手术病例,随机分为甲磺酸罗哌卡因组(n=20)和盐酸罗哌卡因组(n=20)。于给药前和给药后2、5、10、20、30、45、60、90、120、180、240、300、360、720、1 440 min抽取肘前静脉血,采用反相高效液相色谱紫外法,测定血浆中甲磺酸或盐酸罗哌卡因浓度。采用DAS 2.0软件计算药代动力学参数,并比较两组药代动力学参数的特征。结果甲磺酸罗哌卡因和盐酸罗哌卡因组的表观分布容积(Vd/F)分别为(2.1±0.7)和(2.7±1.1)L/kg,消除半衰期(T1/2β)分别为(333±89)和(378±112)min,药时曲线下总面积(AUC0-∞)分别为(480±168)和(425±126)mg.min/L,清除率(CL/F)分别为(4.6±1.3)和(5.1±1.3)mL/(min.kg),达峰时间(Tpeak)分别为(26±13)和(29±20)min,峰浓度(Cmax)分别为(1 732±833)和(1 345±341)ng/mL,两组药代动力学参数比较差异无统计学意义(P>0.05)。结论 0.894%甲磺酸罗哌卡因和0.75%盐酸罗哌卡因药代动力学特征近似,符合二室模型;盐基的改变对罗哌卡因的代谢无影响。

Objective To compare the pharmacokinetics between 0.894% ropivacaine methanesulfonate and 0.75% ropivacaine hydrochloride. Methods Forty patients undergoing lower abdominal or lower limb surgery were randomly divided into ropivacaine methanesulfonate group(n=20) and ropivacaine hydrochloride group(n=20).Blood samples were collected from an antecubital vein before administration and 2,5,10,20,30,45,60,90,120,180,240,300,360,720 and 1 440 min after administration,and the concentrations of ropivacaine methanesulfonate or ropivacaine hydrochloride were determined by reversed phase high performance liquid chromatography-ultraviolet method.The pharmacokinetic parameters were calculated by DAS 2.0 software and were compared between groups. Results The apparent volumes of distribution(Vd/F) of ropivacaine methanesulfonate and ropivacaine hydrochloride were(2.1±0.7) L/kg and(2.7±1.1) L/kg,respectively;the elimination half life time(T1/2β) were(333±89) min and(378±112) min,respectively;the total areas under the concentration-time curve(AUC0-∞) were(480±168) mg·min/L and(425±126) mg·min/L,respectively;the clearance rates(CL/F) were(4.6±1.3) mL/(min kg) and(5.1±1.3) mL/(min kg),respectively;the peak time(Tpeak) were(26±13) min and(29±20) min,respectively;and the maximum concentrations(Cmax) were(1 732±833) ng/mL and(1 345±341) ng/mL,respectively.There was no significant difference in pharmacokinetic parameters between groups(P>0.05). Conclusion The pharmacokinetics of 0.894% ropivacaine methanesulfonate are similar to those of 0.75% ropivacaine hydrochloride,and the pharmacokinetic data are consistent with two-compartment model.In addition,the metabolism of ropivacaine is not influenced by the change of base.