摘要
背景：口服环孢素A的生物利用度和药代动力学个体差异大,故进行药物血药浓度监测,对安全、有效地用药和减少急性排斥反应具有重要临床意义。目的：建立心脏移植后环孢素A血药浓度监测方法,分析药物浓度与剂量、疗效的关系,建立最佳给药方案。设计、时间及地点：样本对照观察,2003-08/09在广西医科大学第四附属医院药剂科临床药学实验室完成。对象：广西壮族自治区首例心脏移植患者,环孢素A胶囊、强的松、霉酚酸酯三联用药治疗。方法：受者早上服药前取静脉血3mL,肝素抗凝,混匀。在10mL具塞玻璃试管内加入内标环孢素B贮备液10μL,加入1mL全血,再加入0.2mol/LNaOH溶液1mL,混匀。取上清液加入另一试管,于60℃水浴挥干,冷却至室温,残渣加入0.05mol/L盐酸与乙腈混合液100μL溶解,再加入400μL正己烷洗涤,离心5min,取下层液20μL进样。运用高效液相色谱法以环孢素B为内标、214nm处紫外检测,对心脏移植受者进行环孢素A血药浓度监测,并及时给予用药剂量调整。主要观察指标：患者是否出现急性排斥反应,环孢素A血药谷浓度。结果：受者高效液相色谱法分析有很好的分离度,环孢素A绝对回收率均不低于75%。监测结果显示环孢素A药物最高浓度产生在移植后第10天,根据结果及时调整用药剂量,移植后14d谷浓度维持在200-300μg/L,受者未出现急性排斥反应。结论：高效液相色谱法能满足心脏移植后环孢素A的血药浓度监测需求,心脏移植后短期环孢素A血药谷浓度维持在200-300μg/L较适合。
BACKGROUND：Due to the difference in bioavailability and pharmacokinetics of cyclosporine A（CsA）among different individu-als,it is of great importance to carry out blood drug concentration monitoring for safety,effectiveness and reduction of acute immunological rejection.OBJECTIVE：To develop a method of blood drug concentration determination of CsA after the heart transplantation,and to ana-lyze the correlation between dose,outcome and concentration so as to develop an optimal administration scheme.DESIGN,TIME AND SETTING：Controlled sample observation was conducted between August and September 2003 at the Clinical Pharmaceutic Laboratory,Fourth Affiliated Hospital,Guangxi Medical University.PARTICIPANT：Heart transplantation patient in the Guangxi Zhuang Autonomous Region was treated with CsA capsule,predni-sone and mycophenolate mofetil.METHODS：3 mL venous blood was taken from the receptor before taking medicine in the morning.As an anticoagulant,heparin was added and misced bene.10 μL CsB,the in internal standard fluid was inserted into a 10 mL glass tube,which was added with 1 mL whole blood and 1 mL NaOH（0.2 mol/L）and misced bene.The supernatant was put into another tube and dried out at 60 ℃,again cooled to room temperature and added with 100 μL solution of 0.05 mol/L acid hydroc and acetonitrile plus 400 μL N-hexane,which was centrifuged for 5 minutes,and 20 μL from lower layer was taken for sample injection.A high efficiency liquid chromatography was used with cyclosporine-B as the internal standard,the patient blood concentration of CsA was detected at 214 nm and the dose was adjusted accordingly.MAIN OUTCOME MEASURES：Whether patients occurred acute rejection or not,and blood drug concentration of CsA were measured.RESULTS：High efficiency liquid chromatography showed good resolving power.The absolute recoveries were not lower than 75%.Monitoring results demonstrated that the highest concentration occurred 10 days after transplantation.The dose was regu-lated according to results.
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2009年第44期8783-8786,共4页
Journal of Clinical Rehabilitative Tissue Engineering Research
