AxSYM与TDx测定环孢素A血药浓度相关性

目的:研究AxSYM与TDx两种方法测定环孢素A(CsA)血药浓度结果相关性.方法:利用AxSYM和TDx两种方法同时测定CsA血药浓度,以TDx测定值为X,AxSYM测定值为Y,进行线性回归,评价其相关性.对于服药后2 h浓度(C2)的测定结果,按在线性范围和超出范围两种情况对AxSYM测定值分别进行评价.结果:TDx测定值均比AxSYM高,测定C0时,TDx/AxSYM为(1.22±0.16),两种方法的相关性较好,回归方程:Y=-15.517 2 0.953 2X(n=108,r=0.993 8);AxSYM法在线性范围内测定C2时,TDx/AxSYM为(1.12±0.04),方法相关性较好,回归方程:Y=17.175 2 0.863 3X(n=46,r=0.992 9),超出线性范围测定C2时,TDx/AxSYM 为(1.18±0.07),方法相关性较差,回归方程:Y=154.076 9 0.727 6X(n=37,r=0.972 7).结论:AxSYM测定CsA血药浓度结果较TDx偏低,对母体药物专属性更好,二者具有较好相关性,适用于CsA血药浓度的常规监测.     

AxSYM替代TDXFLX应用于环孢素血药浓度检测的可行性研究

目的:研究AxSYM与TDXFLX两台仪器测定环孢素(cyclosporin,CsA)血药浓度结果的相关性,评价AxSYM替代TDXFLX用于常规治疗药物监测的可行性。方法:收集第二军医大学长海医院门诊和住院共113例肾移植和造血干细胞移植病人的血样,在同一天内用AxSYM和TDXFLX两种仪器同时测定CsA的血药浓度。以TDXFLX测定值为x,以AxSYM测定值为y,进行相关回归分析,评价其相关性。对测定值x和y进行配对t检验,P<0.05为差异有统计学意义。结果:AxSYM和TDXFLX测定的CsA血药浓度相关性良好,线性方程为y=1.001 9x-6.101 7(n=113,r=0.988 3)。AxSYM测定值比TDXFLX测定值平均低4.76%,有显著性差异(n=113,P<0.05)。结论:AxSYM可以替代TDXFLX用于本院临床CsA的血药浓度检测。     

心脏移植术后早期环孢素A血药浓度测定分析

目的:探讨心脏移植术后早期环孢素A的使用.方法:监测8例原位心脏移植受者术后早期体内环孢素A的全血谷浓度,并对结果进行分析.结果:心脏移植术后早期受者体内环孢素A血药浓度波动幅度大而不规则,其影响因素包括体液的外泄、支持治疗、多种药物的使用、患者肝肾功能等.结论:应及时调整环孢素A的给药剂量,控制CsA血药浓度在有效范围.     

固相萃取RP-HPLC法与AxSYM法测定全血环孢素的相关性分析

目的 分析固相萃取RP-HPLC法与AxSYM法测定环孢素血药浓度结果相关性.方法 分别采用固相萃取RP-HPLC和AxSYM两种方法同时测定100人份环孢素血药浓度,测定值采用t检验进行差异性分析,同时以RP-HPLC法测定值为自变量X,以AxSYM法测定值为因变量Y进行线性回归,评价两者的相关性.结果 采用AxSYM法所测得的血药浓度值较RP-HPLC法的测定值明显偏高,CAxSYM/CRP-HPLC=1.31±0.27(n=100);100人份数据经线性回归得一元线性回归模型:(Y)AxSYM=0.958XRP-HPLC+48.966,(r=0.971,P<0.001).结论 RP-HPLC法的测定值较AxSYM法的测定值明显偏低,但二者具有显著相关性,且呈正相关关系,通过线性回归预测模型,可由RP-HPLC法的测定值估算出AxSYM法的预测值,适用于环孢素的血药浓度测定.     

两种单克隆抗体荧光免疫偏振法测定人全血中环孢素浓度的比较

目的：考察TDx与AxSYM单克隆抗体荧光免疫偏振法测定全血中环孢素A浓度结果的差异。方法：采集12名肾移植患者服药后12h内不同时间点的血样。样本分别用TDx与AxSYM进行测定。测定结果通过均数比较、Passing—Bablok回归法和Bland-Altman偏差图法进行分析。结果：TDx和AxSYM两法的测定结果相关。服药后0．5～4h的血样，两法测定结果差异无显著性。而服药6h后两法的测定结果差异有显著性，且TDx的测定结果高于AxSYM。结论：TDx与AxSYM法测定人全血中环孢素浓度的结果有差异，且与采样时间有关。     

48例难治性肾病综合征患者治疗药物环孢素A血药浓度监测结果分析及其临床意义

目的:分析难治性肾病综合征患者治疗药物环孢素A(CsA)血药浓度监测结果及临床意义。方法:选取2017年4月—2019年4月间收治的难治性肾病综合征患者48例资料,均接受CsA治疗,统计其采用全自动免疫分析仪监测CsA血药浓度的结果,并分析CsA血药浓度与疗效、不良反应的关系。结果:48例难治性肾病综合征患者中CsA血药浓度在100～150 ng/mL范围内所占比例高于CsA血药浓度>150 ng/mL和<100 ng/mL(P<0.05);有效者CsA血药浓度<100 ng/mL所占比例低于无效者(P<0.05);不良反应发生者CsA血药浓度>150 ng/mL所占比例高于无不良反应者(P<0.05)。结论:CsA血药浓度的变化可影响其疗效及安全性,临床治疗中应重点监测CsA血药浓度,据此制定个体化给药方案,以确保难治性肾病综合征患者的治疗效果,减少不良反应的发生。     

肾移植术后环孢素血药浓度监测指标的探讨

目的探讨肾移植受者环孢素(CsA)满意的血药浓度监测指标。方法采用荧光偏振免疫(FPIA)法,对136例肾移植受者进行全血中CsA谷浓度(ρ0)及服药后2 h血药浓度(ρ2)监测,并对数据进行归纳分析。结果肾移植术后2 a内ρ0均值为(221.54±100.41)μg.L-1,ρ2均值为(963.91±379.43)μg.L-1,ρ0 ρ2均值为(1 185.44±433.14)μg.L-1,ρ2/ρ0均值为(4.80±2.29)。结论ρ0 ρ2和ρ2/ρ0作为CsA血药浓度监测指标,能更全面反映CsA体内药物暴露情况和监测CsA肝肾毒性,作为环孢素A血药浓度监测指标是合理的。     

EMIT与FPIA法测定肾移植术后患者体内环孢素A血药浓度结果比较

目的 比较酶扩大免疫法（EMIT）和荧光偏振免疫法（FPIA）监测环孢素A（CsA）血药浓度的相关性.方法 收集肾移植患者服药后达稳态的谷浓度血样,分别用EMIT法和FPIA法进行测定,考察两种方法测定结果的相关程度.结果 两种方法测定结果高度相关,差异有显著性.结论 EMIT法和 FPIA法测定CsA血药浓度结果差异具有统计学意义,在CsA治疗药物监测中应予以关注并作相应调整.     

环孢素A用于银屑病治疗的血药浓度监测追溯分析

目的:评价环孢素A(cyclosporine A,CsA)血药浓度监测对临床银屑病治疗的有效监护作用。方法:收集2018—2020年中国医学科学院皮肤病医院161例采用CsA治疗的银屑病住院患者的资料,对性别、年龄、剂量、联合用药等与CsA血药浓度的相关影响进行比较分析。结果:161例患者共监测CsA血药浓度288例次,平均1.79次/例,平均CsA血药浓度为(123.23±49.72)ng/ml。女性患者的平均CsA日剂量明显高于男性患者,差异有统计学意义(P=0.013);男女患者平均CsA血药浓度比较,差异无统计学意义(P>0.05)。不同年龄段患者CsA血药浓度的差异有极显著统计学意义(P<0.001),日剂量的差异也有统计学差异(P<0.05)。不同类型银屑病患者CsA血药浓度的差异无统计学意义(P>0.05)。联合应用大环内酯类抗菌药物、钙通道阻滞剂、中药丹参等会影响CsA的血药浓度。结论:年龄、联合用药和食物都可能对CsA的血药浓度产生影响。临床应加强血药浓度监测,通过监测结果制订个体化给药方案,提高临床用药的安全性和有效性。     

苯巴比妥降低肝移植患者CsA全血谷浓度的个案报道

环孢素A(cyclosporine,CsA)是器官移植患者临床常用的强效免疫抑制剂之一,由于其治疗窗狭窄,药动学参数个体差异大,容易产生肝肾毒性等严重不良反应,并且CsA血药浓度与其不良反应密切相关,需定期监测血药浓度,进行个体化给药.我院自开展CsA血药浓度监测项目以来,坚持对器官移植患者进行药学随访,笔者在随访过程中发现CsA血药浓度受药物苯巴比妥的影响,现报道如下.     

Stereospecificity of antibody: quinine, the optical isomer of quinidine and anti-malarial drug chloroquine do not cross-react with quinidine immunoassays

Quinine is an optical isomer of quinidine. Both quinine and chloroquine (an aminoquinoline derivative) are used in treating malaria. The authors studied cross-reactivity of quinine and chloroquine with the quinidine immunoassays using the TDx and AxSYM analyzers (Abbott Laboratories, Abbott Park, IL). The authors observed no cross-reactivity of chloroquine with quinidine immunoassays (TDx and AXSYM) even when drug-free serum was supplemented with 1000 microg/mL chloriquine. The authors observed no cross-reactivity of quinine up to a concentration of 250 microg/mL. At higher concentrations, the authors observed a small cross-reactivity. The cross-reactivity of a substance should be studied in the presence of the primary analyte. When serum pools prepared from patients receiving quinidine were supplemented with various concentrations of quinine or chloroquine, the authors observed statistically significant declines in quinidine concentrations with higher concentrations of both quinine and chloroquine. The authors observed significant cross-reactivity of L-amphetamine with the amphetamine immunoassay also marketed by Abbott Laboratories and run on the AxSYM analyzer. The authors conclude that although the antibody used in the quinidine assay is stereospecific, the antibody used in the amphetamine assay by the same manufacturer is not stereospecific.     

Evaluation of the AxSYM monoclonal cyclosporin assay and comparison with radioimmunoassay

Recently, a semiautomated fluorescence polarization immunoassay (FPIA) for determination of parent cyclosporin (CsA) has been developed for the Abbott AxSYM system. The new CsA assay measures the drug from an extracted whole blood specimen. The authors report here the evaluation of this new assay and the comparison with a previously validated radioimmunoassay (RIA) method (CYCLO-Trac SP). To assess the imprecision, the authors used tri-level controls supplied by both Abbott and Bio-Rad manufacturers. The within-run CV ranged from 4.4% to 7.3% and the between-day CV ranged from 4.4% to 7.6%. Mean recovery of the drug from clinical specimens spiked with kit calibrators was 108.4%. Fluorescence polarization immunoassay AxSYM (y) was correlated to RIA (x) by using 132 trough blood specimens (44 renal, 44 liver, and 44 heart) from transplant recipients and resulted in the following Passing-Bablok linear regression equation: y = 6.7 + 0.97x, r = 0.989, S(x/y) = 12.9. The percentage of overestimation (mean, range) by FPIA AxSYM versus RIA was (3.8%, range -17.7% to 39.1%). The results observed with this new method from follow-up studies in patients during the early course after transplant were not consistently higher than those obtained by RIA. These findings contrast with previously reported results that compared FPIA TDx assay with RIA. The authors conclude that FPIA AxSYM is a precise method for measuring CsA and offers results similar to those obtained by RIA with a marked reduction in assay time.     

Adaptation of total phenytoin reagent pack for measuring free phenytoin levels with the Abbott AxSYM immunoassay analyzer

One hundred and four serum samples submitted to our laboratory for total phenytoin levels were also assayed for free phenytoin levels using the Abbott TDx and AxSYM immunochemistry analyzers (Abbott Laboratories; Abbott Park, IL, U.S.A.). Free phenytoin levels were assessed using ultrafiltrates obtained with the Centrifree Microfiltration system (Amicon, Inc.; Beverly, MA, U.S.A.). There was an acceptable correlation of free phenytoin levels between the two instruments (r = 0.994; mean value of free fraction was TDx = 1.7 microg/mL and AxSYM = 1.6 microg/mL). The mean free phenytoin values correlated well with previously reported values in the literature. Acceptable recovery (88.8%-101.5%) and precision (CV = 2.3%-11.0%) were also obtained. The results of this study indicated that free phenytoin levels can be obtained with acceptable accuracy and precision using the total phenytoin reagents.     

Evaluation of the Abbott TDx for determination of phenobarbital in forensic blood specimens

The Abbott TDx was evaluated for determination of phenobarbital (PB) levels in postmortem (PM) blood. Because hemolysis does not interfere with fluorescence polarization assays, the TDx could be a fast, efficient alternative to gas chromatography (GC). The linearity and precision of the TDx assay were evaluated using postmortem blood that was spiked with phenobarbital and serially diluted. The relationship between nominal and measured values was linear for phenobarbital concentrations up to 150 mg/L (r = 0.999) in two separate postmortem bloods. Precision was excellent with run-to-run coefficients of variation of 10% or less. The TDx results for phenobarbital in spiked PM blood were compared to those determined by GC. An excellent correlation (r = 0.999) between the TDx results and GC results was achieved. PM blood specimens from ten forensic cases were assayed for PB by GC and compared with PB results from the TDx. Comparison of these results also showed good correlation (r = 0.959). These data indicate that the Abbott TDx can be used reliably in the estimation of PB levels in postmortem whole blood samples.     

An evaluation of the cyclosporine and metabolites whole blood TDx assay

The new Abbott TDx cyclosporine and metabolites fluorescent polarization immunoassay procedure provides a 20-min sample turn-around time, using 50 microliters of sample for the analysis of cyclosporine in whole blood. A precipitation agent and a lysing agent are utilized as a pretreatment step. The range of the whole blood assay is from 0 to 2,000 ng/ml, with a sensitivity of 50 ng/ml. Precision studies at 3 control levels provided coefficients of variation of 2.1-4.8% for both assays. In order to compare this assay with the currently used Sandoz polyclonal radioimmunoassay (RIA) method. 200 whole blood samples were obtained from 20 renal, cardiac, and hepatic transplant recipients. The mean whole blood cyclosporine concentrations for samples above the sensitivity level were as follows: TDx 754 ng/ml (+/- 31) and RIA 619 ng/ml (+/- 22). Blood TDx levels correlated strongly with RIA levels, with a regression coefficient of r = 0.915. This new assay provides reliable blood cyclosporine concentrations that correlate well with RIA measurements. This assay offers rapid sample turn-around times, making same-day results for outpatient drug monitoring possible.     

Factors influencing the overestimation of plasma vancomycin concentrations measured by the Abbott TDx technique

The Abbott TDx technique (TDx) has been reported to overestimate the plasma concentration of vancomycin (VCM) in patients with renal failure and also in those with normal renal function. The aim of this study was to investigate factors influencing the overestimation of plasma VCM concentrations measured by TDx compared with high-performance liquid chromatography (HPLC) as a reference technique. First, the precision and accuracy of TDx and HPLC were compared using 5 weighed-in concentrations of VCM. The coefficients of variation (CV) for both TDx and HPLC were less than 3% at weighed-in concentrations of 3.0, 7.5, 15.0, 30.0, and 60.0 microg/mL. The authors did not find overestimation of VCM concentrations by TDx in any weighed-in sample. Next, VCM concentrations measured by TDx were compared with those measured by HPLC in 253 plasma samples obtained from 83 patients receiving VCM. Regression analysis showed that VCM concentrations measured by TDx were closely correlated with those measured by HPLC, with a correlation coefficient of 0.963. Then, the authors divided plasma samples into 2 groups based on the time of sampling, ie, pre- and postdose. The mean TDx/HPLC ratio was significantly higher in the predose group (1.23 +/- 0.22) than in the postdose group (1.11 +/- 0.16) (P < 0.01). An Eksborg plot showed that the TDx/HPLC ratio decreased slightly with increased total bilirubin concentrations in the predose samples. These results indicated that plasma VCM concentrations measured by TDx were influenced by the time of sampling and the plasma bilirubin concentration. The overestimation of VCM concentrations in the predose group may have resulted from metabolites of VCM because the relative concentrations of the metabolites were likely to be greater in the predose group than in the postdose group. Thus, VCM postdose samples may provide useful information in cases in which a good clinical outcome has not been obtained using monitoring of the predose concentration alone.     

Comparison of cyclosporine measurement in whole blood by high-performance liquid chromatography, monoclonal fluorescence polarization immunoassay, and monoclonal enzyme-multiplied immunoassay.

Monitoring of cyclosporine concentrations in whole blood is used routinely as a guide to adjusting dose so as to achieve optimal therapeutic benefit with minimal adverse effects. In the present study, we have compared a specific high-performance liquid chromatography (HPLC) assay with a fluorescence polarization immunoassay (TDx) and an enzyme-multiplied immunoassay (Emit). Both Emit and TDx assays employ a monoclonal antibody to cyclosporin A and therefore have the potential for a high degree of specificity. Blood specimens (EDTA as anticoagulant) were obtained from 113 patients (71 renal transplants, 17 liver transplants, and 25 other categories) taking cyclosporine and analysed by all three methods. There were significant correlations between results for HPLC and Emit (Emit = 10.54 + 1.07 x HPLC; r2 = 0.82, p less than 0.001) and between results for HPLC and TDx (TDx = 9.16 + 1.42 x HPLC; r2 = 0.82, p less than 0.001). Compared to HPLC analysis, 74% and 96%, respectively, of Emit and TDx results were to the left of the line of identity. The TDx monoclonal antibody appears to have a lesser degree of specificity than that used in the Emit assay. Mean concentrations of cyclosporine measured by Emit and TDx were 17% and 51% higher, respectively, than those measured by HPLC. Because of this overestimation, we suggest that both Emit and TDx methods may find their most appropriate use in routine therapeutic monitoring of renal transplant patients in whom metabolite concentrations are less variable over time.     

Comparison of cyclosporine blood levels measured by radioimmunoassay and TDx assay using monoclonal antibodies

Whole blood steady-state trough concentrations of cyclosporine were measured by radioimmunoassay (RIA) and TDx assays employing monoclonal antibodies in 82 samples from 39 renal transplant patients. Intra- and interassay coefficients of variation for the new TDx technique averaged 3.2 and 5.4%, respectively. In the concentration range of 40 to 717 ng/ml, there was a linear correlation (r = 0.884, p less than 0.001) between both assays [slope of 0.863; y intercept (RIA values) = 15 ng/ml], indicating that the methods can be used interchangeably. Since the automated TDx assay is faster and causes less waste problems, this reliable technique offers some definite advantages for routine clinical use.     

用HPLC法和TDx法测定卡马西平血清浓度的相关性研究

目的 :研究用HPLC法和TDx法测定卡马西平血清浓度的相关性。方法 :分别用HPLC和TDx测定39例癫痫患者的卡马西平血清浓度 ,比较两种方法的测定结果。结果 :HPLC法 (Y)与TDx法 (X)测定的卡马西平血清浓度的回归方程为Y=1 0616X—0 4677(r=0 9294) ,两种方法在统计学上无显著性差别 (P>0 05)。结论 :用HPLC法和TDx法测定卡马西平血清浓度具有良好的相关性 ,在无TDx血药浓度测定仪时 ,HPLC可作为测定卡马西平血清浓度的常规方法。