276例次肝移植患者西罗莫司血药浓度监测及临床应用分析

Analysis of therapeutic drug monitoring and clinical application of sirolimus in liver transplantation recipients

目的:对西罗莫司(SRL)在肝移植患者免疫抑制治疗过程中的转换治疗及给药方案、血药浓度与给药剂量的关系,以及血药浓度的影响因素等方面进行探讨。方法:选择60例应用SRL做转换治疗的肝移植患者,记录患者各项生理指标,转换治疗方案,SRL谷浓度,肝肾功能,不良反应等。结果:SRL稳态血药谷浓度<5ng·mL-1为102例次,占总血药谷浓度的37.0%;5～15ng·mL-1为170例次,占61.6%;>15ng·mL-1为4例次,占1.4%。患者SRL的谷浓度与剂量/体质量密切相关。影响SRL血药谷浓度的因素依次为剂量/体质量、年龄、Cr。SRL转换治疗前后肾功能变化无显著性(P>0.05),肾功能异常的肝移植患者转换治疗后肾功能较转换治疗前明显好转(P<0.05)。对16例合并FK506患者的研究结果显示FK506撤除前后SRL的C/剂量/体重指标无显著性变化(P>0.05)。5～15ng·mL-1组与<5ng·mL-1组相比,血脂异常的发生率也有升高的趋势。结论:SRL在用药时应密切监测患者血药浓度,及时调整用药剂量使血药浓度维持在有效浓度范围。肾功能异常的患者应用SRL有利于肾功能的恢复。在与FK506合用时应同时监测FK506的血药浓度,保证患者体内免疫抑制剂的浓度维持在有效浓度范围。用药的同时应严密监测患者血脂水平,及时对SRL引起的高血脂症进行治疗。

OBJECTIVE To discussing the conversion therapy and dosage regimen, the relationship between dose and blood concentration, the factors influencing on the plasma concentration, etc. during the immunosuppression treatment about sirolimus in liver transplant recipients. METHODS 60 cases of liver transplantation recipients were enrolled using sirolimus using sirolimus as conversion therapy. The The physiological datas, the conversion therapy, sirolimus trough concentrations, liver and kidney functions and adverse effects of the recipients were recorded. RESULTS There were 102 cases of sirolimus steady - state trough blood concentration below 5 ng mL-1, which made up 37.0% of the total blood trough concentration. 170 cases of sirolimus steadystate trough blood concentration were from 5 ng mL-1 to 15 ng.mL-1, which made up 61.6% of the total blood trough concentration. 4 cases of sirolimus steady-state trough blood concentration were above 15 ng mL-1, which made up 1.4% of the total blood trough concentration. The trough concentration of sirolimus in patients was closely related to the dose/body weight. The factors affecting on sirolimus trough blood concentration were dose/weight, age and Cr. Renal function before and after sirolimus conversion therapy showed no significant change （P〈 0.05）. Renal dysfunction in liver transplantation patients with conversion therapy improved significantly after conversion therapy （P〈0. 05）. The results of a study of 16 patients using both FK506 and sirolimus showed there was no significant change in the C/dose/body weight before and after the removal of FK506 showed no significant change （P〉0. 05）. Compared with the low concentration group, the incidence of abnormal blood lipid of the higher serum concentration group had the tendency to increase. CONCLUSION The plasma concentration of sirolimus should be closely monitored during treatment. the dosage of sirolimus should be adjusted to keep the concentration at the range of the effective blood concentration. Sirolimus helps the recovery of renal function in patients with renal dysfunction. When combined with the FK506, it is necessary of simultaneous monitoring of FK506 blood con eentration, to ensure the concentration of immunosuppressive drugs in patients maintaining at the effective concentration range. The lipid levels should be closely monitored when using sirolimus. Hyperlipidemia caused by sirolimus should be treated in time.