| 引用本文: | 陈岚,贺晴,阮钧.肾移植术后环孢素A血药浓度监测及其体内吸收评价[J].中国现代应用药学,2010,27(5):466-468. |
| .Cyclosporine Absorption Profiling and Therapeutic Drug Monitoring in Stable Renal Allograft Recipients[J].Chin J Mod Appl Pharm(中国现代应用药学),2010,27(5):466-468. |
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| 摘要: |
| 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。 |
| 关键词: 吸收 血药浓度监测 微乳化环孢素 肾移植 |
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| Cyclosporine Absorption Profiling and Therapeutic Drug Monitoring in Stable Renal Allograft Recipients |
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CHEN Lan HE Qing RUAN Jun
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| Abstract: |
| OBJECTIVE Therapetic drug monitoring for cyclosporine microemulsion (CsA-ME) is often performed using trough levels (C0) or levels at 2 h post-dose (C2). This analysis assessed changes in C0 and C2 and their relationship to CsA-ME dose over one year post-transplant in renal transplant patients. METHODS All 92 post-transplant patients in whom C0 and C2 were available at month 1, 3, 6, 12 were measured by FPIA. Normalized dose (ND) of CsA-ME, defined as dose per kilogram body weight, was caculated, together with C0/ND, C2/ND and C2/C0. RESULTS Both C0/ND and C2/ND increased between month 1 and 3: C0/ND increased from 43±15 to 56±20 (ng·mL-1)/(mg·kg-1) and C2/ND increased from 129±62 to 212±80 (ng·mL-1)/(mg·kg-1). Between month 3 and 12, C2/ND remained stable but C0/ND decreased to 48±15 (ng·mL-1)/(mg·kg-1) while the C2/C0 ratio increased from 4.5±1.9 to 5.2±2.3, indicating an acceleration of drug elimination. The inter-individual coefficient of variation was higher for C2/ND than for C0/ND at month 3 and 12. CONCLUSION CsA-ME clearance accelerates between month 3 and 12 post-transplant, resulting in lower C0 levels for a given exposure. As a consequence, C0 monitoring may not progressively underestimate CsA-ME exposure during the first year post-transplant. C2 monitoring contributes to improve individualized CsA-ME treatment beyond month 3. |
| Key words: absorption therapeutic drug monitoring cyclosporine microemulsion renal transplantation |
