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目的探讨肾移植术后稳定患者口服微乳化环孢素A(CsA-ME)的剂量与其血药浓度谷值(C0)和给药后2 h的血药浓度(C2)的关系及其随时间的变化趋势,从而评价CsA-ME的体内吸收过程。方法采用荧光免疫偏振法(FPIA)对92例肾移植患者术后不同时间内测定全血中环孢素A的C0和C2浓度,并分别与每位患者每日每千克体重的用药剂量(ND)相比,得出其相应的浓度(即C0/ND,C2/ND)。计算C2/C0比值并对所得数据进行统计分析。结果肾移植患者术后1~3个月内,C0/ND和C2/ND均增加。C0/ND从(43±15)增加到(56±20)(ng.mL-1)/(mg.kg-1),C2/ND从(129±62)增加到(212±80)(ng.mL-1)/(mg.kg-1),表明药物的吸收逐渐增加。但术后3~12个月内,C2/ND维持原有水平,C0/ND则逐渐降低为48±15(ng.mL-1)/(mg.kg-1),C2/C0比值则从4.5±1.9逐渐增加至5.2±2.3,表明药物在体内的消除代谢逐渐增加。术后3~12个月内,C2/ND的个体间变异系数明显小于C0/ND的个体间变异系数。结论肾移植患者服用CsA-ME在术后3~12月内,其环孢素A在体内的累积清除率逐渐增加,表明术后一年内单纯用C0作为监测指标已不能准确预测CsA-ME在体内的药物暴露总量,应结合C2监测对于提高个体化的治疗将更有临床意义。
Objective To investigate the relationship between the dose of oral microemulsified cyclosporin A (CsA-ME) and the plasma concentration (C0) and the plasma concentration (C2) at 2 h after renal transplantation in stable patients after renal transplantation. In order to evaluate the in vivo absorption of CsA-ME. Methods C0 and C2 concentrations of cyclosporin A in whole blood were determined in 92 renal transplant recipients at different time points by fluorescence immuno - polarimetry (FPIA) and were compared with the daily dose per kilogram of body weight (ND) Compared to the corresponding concentration (ie C0 / ND, C2 / ND). The C2 / C0 ratio was calculated and the resulting data was statistically analyzed. Results Within 1 to 3 months after operation, C0 / ND and C2 / ND increased. C0 / ND increased from (43 ± 15) to (56 ± 20) ng.mL-1 / mg.kg-1 and from 212 ± 80 to 212 ± 80 mL-1) / (mg.kg-1), indicating a gradual increase in drug absorption. However, C2 / ND maintained its original level within 3 to 12 months after operation, while C0 / ND decreased to 48 ± 15 (ng.mL-1) / (mg.kg-1) and C2 / C0 decreased from 4.5 ± 1.9 gradually increased to 5.2 ± 2.3, indicating that the elimination of drugs in the body gradually increased metabolism. Within 3 to 12 months after operation, the coefficient of variation between individuals with C2 / ND was significantly lower than that between individuals with C0 / ND. Conclusion The cumulative clearance rate of CsA-ME in renal transplant recipients from 3 to 12 months after operation was gradually increased, indicating that CsA-ME alone can not be accurately predicted in one year after the operation with C0 as a monitoring indicator The total amount of drug in the body that should be combined with C2 monitoring will be more clinically relevant for improving individualized treatment.