CAJ | 학술논문

目的分析肝移植术后早期他克莫司(Tac)的药动学特征及其结果的干扰因素.方法收集2007年6月至2008年3月间56例成人肝移植受者的全血样本100份,分别用酶联免疫吸附试验(ELISA)法和高效液相色谱-质谱联用(LC/MS/MS)法检测其血Tac浓度,评价两种方法检测的相关性.另外收集50例肝移植受者术后早期(15d内)的血液样本,也用两种方法检测血Tac浓度,同时记录移植后时间、红细胞压积及临床检验结果,分析肝移植后早期Tac的药动学特征及其结果的干扰因素.结果肝移植后1个月内两种方法测定的药物浓度结果间的相关系数为0.5312,1个月后相关系数为0.6875.血Tac浓度＜10μg/L时,ELISA法测定的结果与LC/MS/MS法测定的结果间的相关性较好(相关系数为0.4508,P＞0.05);血Tac浓度≥10 μg/L时,与LC/MS/MS法测定的结果相比较,ELISA法测定的结果偏高(P＜0.05).30％的肝移植早期受者的Tac药动学曲线呈平台型,以药物体内滞留时间(MRT)延长、浓度谷值(Cmin)升高为特征,此类受者采用ELISA法测定的Tac浓度与时间曲线下面积(AUC)的相关性较差,其Cmin和AUC分别较用LC/MS/MS法测定的结果升高19.4％和20.1％.Cmin的交叉反应性与肝功能恢复延迟有关;药物MRT延长与总胆红素升高、低红细胞压积相关.结论肝移植后早期他可莫司的药动学表现多样而复杂,检测方法及机体恢复状况均可以影响浓度谷值的测定结果,测定浓度-时间曲线下面积比单纯测定浓度谷值对临床药物剂量的调整更具指导意义.
목적 분석간이식술후조기타극막사(Tac)적약동학특정급기결과적간우인소.방법 수집2007년6월지2008년3월간56례성인간이식수자적전혈양본100빈,분별용매련면역흡부시험(ELISA)법화고효액상색보-질보련용(LC/MS/MS)법검측기혈Tac농도,평개량충방법검측적상관성.령외수집50례간이식수자술후조기(15d내)적혈액양본,야용량충방법검측혈Tac농도,동시기록이식후시간、홍세포압적급림상검험결과,분석간이식후조기Tac적약동학특정급기결과적간우인소.결과 간이식후1개월내량충방법측정적약물농도결과간적상관계수위0.5312,1개월후상관계수위0.6875.혈Tac농도＜10μg/L시,ELISA법측정적결과여LC/MS/MS법측정적결과간적상관성교호(상관계수위0.4508,P＞0.05);혈Tac농도≥10 μg/L시,여LC/MS/MS법측정적결과상비교,ELISA법측정적결과편고(P＜0.05).30％적간이식조기수자적Tac약동학곡선정평태형,이약물체내체류시간(MRT)연장、농도곡치(Cmin)승고위특정,차류수자채용ELISA법측정적Tac농도여시간곡선하면적(AUC)적상관성교차,기Cmin화AUC분별교용LC/MS/MS법측정적결과승고19.4％화20.1％.Cmin적교차반응성여간공능회복연지유관;약물MRT연장여총담홍소승고、저홍세포압적상관.결론 간이식후조기타가막사적약동학표현다양이복잡,검측방법급궤체회복상황균가이영향농도곡치적측정결과,측정농도-시간곡선하면적비단순측정농도곡치대림상약물제량적조정경구지도의의.
Objective To explore the main factors that make it difficult to empirically monitor tacrolimus (Tac) in the early period post-liver transplantation (post-LT),with a specific focus on those aspects related to immunoassay method and pharmacokinetic (PK) assumptions as well as clinical status on which drug individualization in clinical practice is based.Methods 100 whole blood samples from 56 adult liver transplant patients between June 2007 and March 2008 were collected.All blood samples were tested for Tac through levels using ELISA and LC/MS/MS methods were used to evaluate the accuracy of ELISA.Another 50 de novo LT patients treated twice daily with Tac for up to 15 days were analyzed for their PKs,the post-transplant time,hematocrit,and other clinical parameters during the study period were also recorded to explore their PK realties and most factors that interfered with Tac trough monitoring in their early post-LT period.Results Tac level showed lower correlation (RR=0.5312) between the two methods in early period post-LT.When Tac trough levels were less than 10 μg/L,ELISA method showed fairly good correlation to LC/MS/MS with their results being comparable,however,when Tas trough level exceeded 10 μg/L,ELISA results were much higher and had significant difference to those by LC/MS/MS.30 ％ LT recipients showed “platform” curve of TAC PKs,characterized by higher Cmun and longer MRT values,in which trough level determined by ELISA had a very low correlation to the area under curve (AUC) value,moreover,their trough levels and AUCs were 19.4 ％ and 20.1 ％ higher than those determined by LC/MS/MS,respectively.The prolonged MRT was correlated with elevated T-Bil,and negatively correlated with reduced HCT,suggesting delayed recovery of stability also attributed to lower clearance of Tac.Conclusion There is a variety and complexity of Tac kinetics in early LTs,and test method and clinical status will affect trough result.Besides Cmin,full PK structure and AUC are more reliable as biomarkers to monitor Tac in early post-LT period.