Effect of plasma lipid on pharmacokinetics of ciclosporin and its relationship with plasma prednisolone level in renal transplant patients
Effect of plasma lipid on pharmacokinetics of ciclosporin and its relationship with plasma prednisolone level in renal transplant patients
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DOI：
10.1211/jpp.58.9.0005
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发表时间：
2006-09-01
影响因子：
3.3
通讯作者：
Takada, Kanji
中科院分区：
文献类型：
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作者：
Sugioka, Nobuyuki;Kokuhu, Takatoshi;Takada, Kanji
环孢素(环孢菌素A，CyA)是器官移植后使用的一种有效的免疫抑制剂。CyA的药代动力学性质差异很大，脂蛋白是血浆中CyA的主要络合成分。因此，脂蛋白水平的改变可能会影响CyA的药代动力学性质。强的松龙(PSL)与环磷酰胺(CyA)作为免疫抑制剂联合使用。器官移植后，多观察到PSL治疗引起的高脂血症，PSL升高了血浆脂蛋白水平。因此，为了获得更多有关CyA治疗药物监测(TDM)的有用信息，本研究对血浆PSL水平、血浆脂蛋白水平与血CyA水平之间的关系进行了详细的研究。进行了一项开放标签、非随机、回溯性研究。资料包括2002年至2004年间接受活体亲属肾移植的21名男性和11名女性患者(年龄11-65岁)。在术后第7、14、28天，给予PSL 40 mg后至9h的血药浓度-时间曲线下面积(AUC(PSL40)(0-9))与总胆固醇(T-CHO)(r=0.558、0.768、0.660)、高密度脂蛋白(HDL0.05)(r=0.688，P<；0.05；0.835，P<；0.01；0.508；P<；0.508；与极低密度脂蛋白呈负相关(r=-0.486，P<；0.01；-0.776，P&t；0.01；-0.967，P<；0.01)。此外，CyA给药后9h的AUC(AUC(CyA)(0-9))也与T-CHO(r=0.797，P<；0.01；0.577，P<；0.05；0.901，P<；0.01)、高密度脂蛋白(r=0.514，P<；0.05；0.614，P<；0.05；0.893，P<；0.01)和低密度脂蛋白(r=0.906，P<；0.01；0.573，P<；0.05；0.537，P<；0.05)，与0-9，0-9极低密度脂蛋白呈负相关(r=-0.480，-0.630，-0.632，P均<0.05)。此外，AUC(CyA)(0.728-9)与AUC(PSL40)(0-9)有很好的相关性(r=0.728，P<；0.01；0.482，P<；0.05；0.688，P<；0.05)，即认为血浆PSL浓度的变化通过脂蛋白水平的变化影响了CyA的药代动力学特性。这些结果提示，监测血脂生化指标和血浆PSL水平可能有助于CyA的TDM。
Ciclosporin (cyclosporine A, CyA) is a potent immunosuppressant used after organ transplantation. The pharmacokinetic properties of CyA vary widely and lipoproteins are the major complexing constituents for CyA in the plasma. Therefore, a change in lipoprotein level may influence the pharmacokinetic properties of CyA. Prednisolone (PSL) is concomitantly used with CyA as an immunosuppressant. After organ transplantation, hyperlipidaemia resulting from PSL therapy has been mostly observed and PSL increased the plasma lipoprotein level. Therefore, in this study, to obtain more useful information of the therapeutic drug monitoring (TDM) of CyA, the relationship between the plasma PSL level, plasma lipoprotein level and blood CyA level was investigated in detail. An open-label, non-randomized, retrospective study was performed. Data from 21 male and 11 female patients (age 11-65 years) who received a living-related renal transplantation from 2002 to 2004 were included. On postoperative days (PODs) 7, 14 and 28, the area under the plasma concentration-time curve until 9 h after 40 mg of PSL administration (AUC(PSL40)(0-9)) correlated well with total cholesterol (T-cho) (r = 0.558, 0.768, 0.660, all P < 0.05) and high-density lipoprotein (HDL) (r = 0.688, P < 0.05; 0.835, P < 0.01; 0.508, P < 0.05), and correlated negatively with very-low-density lipoprotein (VLDL) (r = -0.486, P < 0.01; -0.776, P < 0.01; -0.967, P < 0.01). In addition, AUC until 9h after CyA administration (AUC(CyA)(0-9)) also correlated with T-cho (r = 0.797, P < 0.01; 0.577, P < 0.05; 0.901, P < 0.01), HDL (r = 0.514, P < 0.05; 0.614, P < 0.05; 0.893, P < 0.01) and low-density lipoprotein (LDL) (r = 0.906, P < 0.01; 0.573, P < 0.05; 0.537, P < 0.05), and there was a negative correlation with 0-9 0-9 VLDL (r = -0.480, -0.630, -0.632, all P < 0.05). Moreover, AUC(CyA)(0-9) correlated well with AUC(PSL40)(0-9) (r = 0.728, P < 0.01; 0.482, P < 0.05; 0.688, P < 0.05); namely, it was considered that the variety of plasma PSL concentrations influenced the pharmacokinetic properties of CyA through the change in lipoprotein levels. These results suggested that monitoring of the biochemical parameters of the plasma lipid and plasma PSL level might be useful for the TDM of CyA.