| Objective:To observe the effect of CYP3A5 * 3 genotype on the C0 / D of tacrohmus in kidney transplant patients.The efficacy and safety and pharmacoeconomics were studied in a CYP3A5*3genotype to guide kidney transplant patients in a prospective trial.Method:1.Collected from January 2013 to October 2015,127 cases of adult kidney transplant patients,patients were collected basic data,drug concentration data within 2.months after surgery and the first three months after surgery and the CYP3A5 * 1 / * 1 and CYP3A5 * 1 / * 3 genotype were classified as fast Metabolic group,CYP3A5 * 3 / * 3 genotype were classified as slow metabolic group,and compare the two groups drug concentration / drug dose(C0 / D)ratio.2.Through the prospective experiments on the CYP3A5 * 3 genotype to guide patients after renal transplantation with tacrolimus(FK506)the effectiveness and safety,and pharmacoeconomics evaluation in order to provide a reference for future clinical application of tacrolimus.3.60 patients were collected.The CYP3A5 * 3 genotype was determined by pyrosequencing method.60 recipients were randomly divided into two groups: experimental group and control group.Tacrolimus 4.0 mg·d-1 was used on day 1 after renal transplantation.On the third day after operation,the test group needed to be based on the CYP3A5 * 3 genotype [AA and AG were expression type,the dose given was 0.12 mg · kg-1 · d-1,the GG type was non-expression type,0.06 mg · kg-1 · d-1] to adjust the dose of tacrolimus.,follow-up period of 1 year.The parameters were recorded,and then through the data,pharmacoeconomics evaluation in order to provide a reference for future clinical application of tacrolimusResult:1.C0/D in CYP3A5*1-carried patients was also lower than CYP3A5*1 unexpressed patients(all P<0.05).At day 5 after the transplant,significantly more patients in the experiment group were within the tacrolimus target C0 range(90%(27/30))as compared to the control group(46.67%(14/30)(P<0.05).At this time point,the median tacrolimus C0 was 5.08(2.5–8.7)μg·L-1 in the experiment group vs 5.29(1.3–13.6)μg·L-1 in the control group(P<0.05).When C0/D was analyzedaccording to CYP3A5*3 genotype,we found the mean C0/D in the both group with CY3A5*3/*3 >CYP3A5*3/*1 > CYP3A5*1/*1.It is note that the time to achieve target TAC(4.40±0.97)in the experiment group,as compared time to achieve target TAC(7.57±3.42)in the control group.In total,the number of daily dose modifications was 11 in the experiment group and 49 in the control group in two weeks after transplantation(P<0.05).Renal function at day 14 after transplantation and adverse events during 12 M of follow-up were similar in both groups.In total,10 adverse events were reported in the experiment group and 11 in the control group(P>0.05).The results of cost-effectiveness analysis showed that experiment group cumulative costs and effects were ￥38067 and 0.90 quality-adjusted life years gained.Control group cumulative costs and effects were ￥38681and 0.87 quality-adjusted life years gained.In the base case analyses,experiment group was more cost-effective.Conclusion :Those findings suggest that the CYP3A5*1 genotype contributes to inter-individual variation in the C0/D of tacrolimus in adult renal transplantation.The recipients with CYP3A5* 1 allelic genes need higher dose of tacrolimus to achieve the perfect concentration.Patients can benefit from setting and adjusting FK506 dosage according to CYP3A5 genotype.Individualized adjustment of Tac doses for patients according to recipients different CYP3A5*3 genotypes is beneficial for reaching target concentration as soon as possible and more cost-effective. |
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