Effect of CYP3A4*1G genetic polymorphism on pharmacokinetics of levobupivacaine after epidural administration / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of CYP3A4*1G genetic polymorphism on the pharmacokinetics of levobupivacaine after epidural administration.Methods One hundred and eleven American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients,aged 30-60 yr,weighing 56-79 kg,scheduled for elective lower extremity surgery under epidural anesthesia,were enrolled in the study.Blood sampies were collected from the central vein before anesthesia for detection of CYP3A4*1G genotypes by polymerase chain reaction-restriction fragment length polymorphism.The patients were divided into 3 groups according to the CYP3A4*1G genotypeswild hemozygote (CYP3A4*1/*1) group (w/w group),mutation heterozygote (CYP3A4*1/*1G) group (m/w group) and mutation hemozygote (CYP3A4*1G/*1G) group (m/m group).An epidural catheter was placed at the L1,2 interspace,and 0.75％ levobupivacaine 1.8 mg/kg was injected.Thirty-four patients were randomly selected,and blood samples from the central vein were collected at0,10,20,30,45,60,90,120,180,240,360,480,840 and 1 440 min after administration for determination of plasma concentrations of levobupivacaine by high-performance liquid chromatography.The pharmacokinetic parameters were calculated.Results There were 42 cases in group w/w,59 cases in group m/w,and 10 cases in group m/m.The frequency of CYP3A4*1G variant allele was 35.6％ in the 111 patients underwent lower extremity surgery.There were no significant differences between the three groups in the plasma concentrations of levobupivacaine at different time points,elimination halflife,clearance,distribution volume,elimination rate constant,peak plasma concentration,time to peak plasma concentration or area under the concentration-time curve (P＞0.05).Conclusion CYP3A4*1G genetic polymorphism is not one of the genetic factors contributing to the individual variation in the pharmacokinetics of levobupivacaine after epidural administration.