The Research Of Pharmacokinetics Of Intravenous Lidocaine Hydrochloride Between Dai And Han Population Patients

Baekground Lidocaine is a lactam local anesthetic of medium effect,lidocaine has only enantiomers specificity in the lactam local anesthetics,shows a single structure on the molecular level.Lidocaine onset fast,wide dispersion, penetrating strong,is commonly used in local anesthetic of medium effect. Lidocaine mainly bindsα₁-acid protein in plasma,with the rate of 65%. Lidocaine of N-ethyl generates single-ethyl glycerol dimethylaniline(MEGX), 3-hydroxyl generates 3-OH-lidocaine.Clinical studies show that clinical dose of lidocaine is mainly effected N-ethyl-role by cytochrome P450(CYP)1A2, high-dose mainly effected N-ethyl-role by CYP3A4.3-hydroxylation-role only by CYP1A2.CYP1A2 has gene polymorphism in inter-ethnic,SO that the CYP1A2 activity may have differences,the results of inter-ethnic lidocaine may have some parameters difference of pharmacokinetics.This series of research projected through the first stage of the Han and Dai population polymorphism of the CYP1A2 gene,the result of allele frequencies of CYP1A2-2964 were 0.24 (95%CI:0.2-0 0.3)and 0.34(95%CI:0.30-0.40),respectively,and showed significant differences between Dai and Han population,A2964 in the Dai People was higher incidence than in the the Han(P＜0.05).The second stage will further validate the clinical application of lidocaine between Dai and Han population to determine whether there will be differences in some parameters of the pharmacokinetics. Objective To determine the pharmacokinetics of intravenous lidocaine hydrochloride between Dai and Han patients undergoing surgical operation.Methods 60 unrelated within three generations who are in Xishuangbanna Dai territory hospital were randomly selected Dai(Group D)and Han(Group H),each group of 30 cases,male 15 and 15 female in each group,ASAâ… orâ…¡,no cardiac and hepatorenal dysfunction,aged 20-50 years old,weighing 45-75 kg undergoing elective surgery patients.The patents were unpremedicated.2% lidocaine hydrochloride 1 mg.kg^-1by intravenous injection was given after 30 min of general anesthesia.Blood samples were taken from CVP line at 3,8,15,30 and 45 min after intravenous lidocaine hydrochloride was given for determination of plasma concentration of lidocaine using HPLC,Pharmacokinetic parameters were estimated with DAS program..Results The plasma concentration-time curve of lidocaine hydrochloride pharmacokinetics was fitted to a two-compartment open model.The plasma concentration reached the peak at 3 min,the peak plasma concentration(C_max) was 4.23±0.43 ug.ml^-1largest.There were no significant statistical difference of K₁₀,k₁₂,k₂₁between two groups(P＞0.05).Area under the concentration-time curve[AUC(0-t)],AUC(0-∞),and C_maxwere significantly statistical difference between two groups(P＜0.01).Distribution half-life(t_1/2α),the central chamber volume of distribution(V₁)were significantly statistical difference between two groups(P＜0.05 and P＜0.01,respectively).Elimination half-life (t_1/2β),the clearance rate(CL)were statistically significant differences between two groups(P＜0.05 and P＜0.01,respectively).Conclusions Compared with the Group H,lidocaine plasma concentration decreased significantly in Group D.Group H of the absorption of lidocaine was significantly larger than Group H,AUC(0-t),AUC(0 -∞),and C_maxincreased significantly.C_maxwas 4.23±0.43ug.ml^-1,but less than adults lidocaine poisoning serum concentration of 5.3ug.ml^-1.Group D of the distribution of lidocaine in the body was significantly greater than Group H,t_1/2αprolonged,V₁ increased.The elimination of lidocaine in the body obviously faster than that in Group D Group H,t_1/2βprolonged,CL increased.