The Effect Of WuZhi Capsule On The Tacrolimus's Serum Concentration Of The Patients Undergoing Liver Transplantation With Different CYP3A5 Genotype

Objective:To study the effect of WuZhi capsule on the tacrolimus' s serum concentration of the patients undergoing liver transplantation with different CYP3A5 genotype,and to establish suitable dosage regimen for different genotype in patients with liver transplantation and to guide clinical drug use.Methods:82 cases undergoing transplantation in our hospital from 2015.8 to 2017.9,based on difference of recepients' and donors' CYP3A5,divided into 4 groups: recipients express(1 *)/donors express(1 *)group(EX-R/EX-D)including 18 cases,recipients express(1 *)/donors do not express(1 *)group(EX-R/NEX-D)including 26 patients,recipients do not express(1 *)/donor express(1 *)group(NEX-R/EX-D)including 18 cases,recipients do not express(1 *)/donor do not express(1 *)group(NEX-R/NEX-D)including 20 cases.Comparing and analysising the difference and relevance of tacrolimus dosage,blood drug concentration,blood drug concentration/dose specific value and whether taking Wu Zhi capsule or not between groups,as well as the effect of Wu Zhi capsule on changing tacrolimus dosage,blood drug concentration,blood drug concentration/dose specific value between groups before and after the use of it.Results:Comparision of of tacrolimus dosage between groups,compared with the initial tacrolimus dose in NEX-R/NEX-D group,which is 0.06± 0.02 mg.kg-1.d-1,the initial tacrolimus dose in EX-R/EX-D group is higher which is 0.08±0.02 mg.kg-1.d-1,statistically significant difference(P < 0.05);Comparision of of tacrolimus blood drug concentration between groups,compared with the blood drug concentration in NEX-R/NEX-D group,which is 9.35±4.41ng/ml,the blood drug concentration in EX-R/EX-D group is lower,which is 4.82±1.81ng/ml,statistically significant difference(P < 0.05);The tacrolimus blood drug concentration in EX-R/NEX-D group and NEX-R/EX-D group are 6.67± 2.58ng/ml?5.73±3.06ng/ml,having no statistical significance(P > 0.05)compare to EX-R/EX-D group and having statistical significance(P < 0.05)compare to the NEX-R/NEX-D group;Comparision of of tacrolimus blood drug concentration/tacrolimus dosage specific value(C/D)between groups,compared with the blood drug concentration/tacrolimus dosage(C/D)in NEX-R/NEX-D group,which is 175.32±148.08 ng.kg.d.ml-1.mg-1,the blood drug concentration/ tacrolimus dosage specific value(C/D)in EX-R/EX-D group is lower,which is 61.15±27.92 ng.kg.d.ml-1.mg-1,statistically significant difference(P < 0.05);The tacrolimus blood drug concentration/tacrolimus dosage specific value(C/D)in EX-R/NEX-D group and NEX-R/EX-D group are 87.18±54.50 ng.kg.d.ml-1.mg-1?81.43± 36.60 ng.kg.d.ml-1.mg-1,having no statistical significance(P > 0.05)compare to EX-R/EX-D group and having statistical significance(P < 0.05)compare to the NEX-R/NEX-D group;The proportion of adding Wu Zhi capsule in EX-R/EX-D group,the NEX-R/EX-D group,the EX-R/NEX-D group and NEX-R/NEX-D group are 77.8%(14/18),61.1%(11/18),53.8%(14/26)and 30%(6/20),differences between groups have statistical significance(P < 0.05),that is,The proportion of adding Wu Zhi capsule EX-R/EX-D group > the NEX-R/EX-D group > the EX-R/NEX-D group > NEX-R/NEX-D group,the tacrolimus dose,tacrolimus blood drug concentration and tacrolimus blood drug concentration/tacrolimus dosage specific value(C/D)difference between groups have no statistical significance(P > 0.05)after the use of Wu Zhi capsule.The tacrolimus dose,tacrolimus blood drug concentration/tacrolimus dosage specific value(C/D)difference between before and after the use of Wu Zhi capsule in each group have statistical no significance(P > 0.05),while,the tacrolimus blood drug concentration after adding Wu Zhi capsule in EX-R/EX-D group,the NEX-R/EX-D group,the EX-R/NEX-D group are 8.94±2.79ng/ml?9.51±3.28ng/ml?8.59±3.68ng/ml,compare to before the use of Wu Zhi capsule,which are 4.82±1.81ng/ml?6.67±2.58ng/ml?5.73± 3.06ng/ml,the difference have statistical significance(P < 0.05).Conclusions:1.The difference and relevance of tacrolimus dosage,blood drug concentration,blood drug concentration/dose specific value and whether taking Wu Zhi capsule or not are associated with the recipients' and donors' CYP3A5,preoperative testing for the recipients' and donors' CYP3A5 gene can help in predicting the pharmacokinetics of tacrolimus and providing the reference index for the use of tacrolimus and Wu Zhi capsule individualized.2.CYP3A5 gene for the EX-R/EX-D patients should be given a higher dose of tacrolimus(0.09±0.03 mg.kg-1.d-1),closely monitoring the tacrolimus blood concentrations in the early stage of post-operation.The patients whose tacrolimus concentration less than 5 ng/ml should be given Wu Zhi capsule appropriately to increase blood drug concentration up to the target concentration,so as to prevent the early acute rejection effectively after liver transplantation,at the same time after adding Wu Zhi capsule or changing the dose of the capsule,it is necessary to monitor tacrolimus blood concentrations and adjust the dose of tacrolimus gradually.3.Since Wu Zhi capsule have been used in different genotype group with different rate,patients with large dose of tacrolimus(> 0.1mg.kg-1.d-1)have low blood drug concentration(< 5 ng/ml)should be given Wu Zhi capsule regardless of what kind of genotype,the recommendation of the initial dose is 0.5 g.