环孢素与其3种代谢物的浓度相关性和生物转化的分析

Correlation between cyclosporine A and its metabolites in patients with renal transplantation

目的:测定患者服用环孢素后全血中环孢素及其代谢物浓度,分析环孢素与其3种代谢物的浓度之间的关系,研究环孢素体内代谢规律。方法:30例肾移植患者口服环孢素后12h采用液相色谱-质谱联用仪测定环孢素与其3种代谢物的全血浓度,采用线性回归法计算环孢素与其3种代谢物的浓度相关系数,评价相关性。结果:环孢素与去甲环孢素、羟化环孢素及二羟化环孢素的相关性逐步递增,相关系数分别为0.5151,0.7887,0.8084。羟化环孢素浓度与二羟化环孢素浓度具有较强的相关性,相关系数为0.8651。结论:测定环孢素及其3种代谢产物不仅是延长移植器官在体生存期,避免肝肾性综合体征反应的一种有效的方法,而且对于个体化用药具有重要意义。

Objective: To monitor the blood concentrations of cyclosporine A (CsA) and its metabolites in patients with renal transplantation to assess their correlation of enzyme metabolism to individual difference. Methods:The blood samples from patients with renal transplantation who orally administrated CsA in 12 hours were measured by liquid chromatography tandem mass spectrometry. The correlation coefficient of the blood concentration of CsA with its metabolites was calculated using the linear regression. Results:The analytic results showed an escalated correlation coefficient of CsA with demethyl CsA, hydroxy CsA and dihydroxy CsA (0.5151,0.788 7,0. 8084), respectively. The concentration of hydroxy CsA was correlated with concentration of dihydroxy CsA (coefficient 0.8651). Conclusion:The CsA metabolites may result in major side effects in patents with renal transplantation. Thus, monitoring the concentrations of CsA and its metabolites may provide clinical preventions for the liver renal adverse reactions and rational regimens in individualized administration of CsA.