CAJ | 학술논문

目的研究细胞色素P450 3A5(CYP3A5)*3基因多态性指导肾移植术后他克莫司个体化用药的临床效果.方法术后第1天采用焦磷酸测序法测定肾移植受者CYP3A5*3基因型,并根据基因型将60例受者分为试验组和对照组,首先试验组和对照组均根据经验于术后第1天常规给予他克莫司初始剂量4.0 mg/d.试验组根据CYP3A5*3基因型的不同在术后第3天调整他克莫司的剂量[AA型(表达型)为0.12 mg·kg-1·d-1,GG型(不表达型)为0.06 mg·kg-1·d-1];对照组则按照血他克莫司浓度检测的结果调整他克莫司剂量.比较两组术后第5天达到血他克莫司靶浓度(3～8μg/L)的受者比例、达到靶浓度所需要的时间及2周内调整剂量的次数.结果肾移植术后第5天,试验组达到靶浓度的受者比例为90％,对照组则为46.67％,试验组显著高于对照组(P＜0.05).试验组受者达到血他克莫司靶浓度的时间为(3.67±1.32)d,对照组为(7.57±3.42)d,试验组受者达到血他克莫司靶浓度所需时间显著少于对照组(P＜0.05).术后2周内,试验组受者的调药次数显著少于对照组(P＜0.05),试验组未调药就能达到血他克莫司靶浓度的受者比例高达70％.结论根据CYP3A5*3基因型调整他克莫司剂量优于传统的经验性给药方案,能有效地使各基因型受者在肾移植术后早期迅速达到有效的血他克莫司浓度范围.
목적 연구세포색소P450 3A5(CYP3A5)*3기인다태성지도신이식술후타극막사개체화용약적림상효과.방법 술후제1천채용초린산측서법측정신이식수자CYP3A5*3기인형,병근거기인형장60례수자분위시험조화대조조,수선시험조화대조조균근거경험우술후제1천상규급여타극막사초시제량4.0 mg/d.시험조근거CYP3A5*3기인형적불동재술후제3천조정타극막사적제량[AA형(표체형)위0.12 mg·kg-1·d-1,GG형(불표체형)위0.06 mg·kg-1·d-1];대조조칙안조혈타극막사농도검측적결과조정타극막사제량.비교량조술후제5천체도혈타극막사파농도(3～8μg/L)적수자비례、체도파농도소수요적시간급2주내조정제량적차수.결과 신이식술후제5천,시험조체도파농도적수자비례위90％,대조조칙위46.67％,시험조현저고우대조조(P＜0.05).시험조수자체도혈타극막사파농도적시간위(3.67±1.32)d,대조조위(7.57±3.42)d,시험조수자체도혈타극막사파농도소수시간현저소우대조조(P＜0.05).술후2주내,시험조수자적조약차수현저소우대조조(P＜0.05),시험조미조약취능체도혈타극막사파농도적수자비례고체70％.결론 근거CYP3A5*3기인형조정타극막사제량우우전통적경험성급약방안,능유효지사각기인형수자재신이식술후조기신속체도유효적혈타극막사농도범위.
Objective To investigate the value of Cytochrome P450 (CYP3A5) * 3 gene polymorphism in providing individualized administration for the use of tacrolimus (Tac) in renal transplantation recipients.Method Pyrophosphate sequencing method was used to determine the CYP3A5 * 3 genotype of renal transplant patients in the first day after surgery.Sixty recipients were divided into experiment group and control group.Both groups of patients were routinely given the initial dose of Tac-4.0 mg/day in the first day after surgery.The experiment group of patients were given different doses of Tac based on the different CYP3A5 * 3 genotypes at the third day after surgery [for AA:0.12 mg/(kg· day),and for GG:0.06 mg/(kg· day)],and the control group of patients were given different dosages of Tac according to drug concentration.Different parameters were compared between two groups of patients:percentage of patients reaching the target concentration (3-8 μg/L) at the fifth day after surgery,days required to reach the target concentration level,times needed to adjust the dosage of Tac within two weeks.Result The percentage of patients reaching the target concentration in experiment group and control group was 90％ and 46.67％,respectively (P＜ 0.05).Days required to reach the target concentration were (3.67 ± 1.32) and (7.57 ± 3.42) on average,respectively (P ＜ 0.05).Times of adjusting the Tac dose in experiment group was significantly less than those in the control group (P＜0.05).In the experiment group,the target concentration was obtained even without dosage adjustment (70％).Conclusion Individualized adjustment of Tac doses for patients according to recipients' different CYP3A5 * 3 genotypes is beneficial for reaching target concentration as soon as possible,which is superior to traditional dosage regimen.