移植后高血压与他克莫司剂量及血药浓度的关系

中国临床药理学与治疗学 ›› 2012, Vol. 17 ›› Issue (1): 78-82.

移植后高血压与他克莫司剂量及血药浓度的关系

席兰艳^1,2, 袁洪¹, 成柯³, 朱利军³, 阳国平¹, 张桂香¹, 黄志军¹

¹中南大学湘雅三医院临床药理中心;
²长沙市中心医院药学部;
³中南大学湘雅三医院器官移植中心,长沙 410013,湖南

收稿日期:2011-09-21 修回日期:2012-12-06 出版日期:2012-01-26 发布日期:2012-02-16
通讯作者: 黄志军,男,博士,助理研究员,研究方向:临床药理学。Tel: 0731-88618319 E-mail: mhzj@163.com
作者简介:席兰艳,女,硕士,药师,研究方向:临床药学。Tel: 0731-85668121 E-mail: lanzikx99@163.com
基金资助:
国家重点基础研究发展计划(2011CB512001);湖南省国际合作科技计划重点项目(2010WK2006)

Relationship between post-transplantation hypertension and dose, plasma concentration of tacrolimus

XI Lan-yan^1,2, YUAN Hong¹, CHENG Ke³, ZHU Li-jun³, YANG Guo-ping¹, ZHANG Gui-xiang¹, HUANG Zhi-jun¹

¹Center of Clinical Pharmacology, the Third Xiangya Hospital of Central South University;
²Department of Pharmacy, Changsha Central Hospital;
³Organ Transplantation Center, the Third Xiangya Hospital of Central South University, Changsha 410013,Hunan, China

Received:2011-09-21 Revised:2012-12-06 Online:2012-01-26 Published:2012-02-16

摘要/Abstract

摘要： 目的: 调查肾移植患者服用他克莫司后高血压的发生率,并探讨移植后高血压与他克莫司的服用剂量、血药浓度及血药浓度/剂量的相关性。方法: 选取以他克莫司进行治疗的肾移植患者200例,测量患者的血压。然后从中随机抽取53例高血压患者和53例正常血压患者,待患者服用他克莫司至少3 d后,运用微粒子酶免疫分析(MEIA) 法测定他克莫司谷浓度,分析他克莫司剂量、血药浓度与血压水平的相关性,并比较两组患者的他克莫司剂量、血药浓度及血药浓度/剂量的差异。结果: 在200例肾移植患者中,104例患者(52.0%)患有移植后高血压;他克莫司日剂量与患者的SBP呈正相关(r=0.216,P＜0.05),而剂量与DBP,血药浓度与血压水平均无相关性;高血压组他克莫司的服用剂量明显高于正常血压组[(3.11±1.49) mg/d∶(2.42±1.07) mg/d,P＜0.05];谷浓度两组间比较差异无统计学意义(P＞0.05);高血压组患者的谷浓度/剂量明显低于正常血压组[(2.94±1.57) ng·d/mg·mL∶(3.95±3.02) ng·d/mg·mL,P＜0.05]。结论: 肾移植患者的SBP与他克莫司日剂量具有明显相关性,服用更高剂量他克莫司的患者更易发生高血压。

关键词: 肾移植, 高血压, 他克莫司, 剂量, 血药浓度

Abstract: AIM: To investigate the incidence of hypertension after renal transplantation in patients administered with tacrolimus, and the correlation among blood pressure, tacrolimus dosage, plasma concentration and concentration/dose ratio of tacrolimus.METHODS: 200 renal transplant patients treated with tacrolimus were screened in the study, and the blood pressure were measured.Fifty-three hypertensive patients and Fifty-three normotensive patients were randomly enrolled from all screened patients.Tacrolimus was administrated at a stable dose for at least 3 days.Tacrolimus trough level was determined by Microparticle Enzyme Immunoassay (MEIA). The association of blood pressure in tacrolimus dosage and concentration were analyzed. Meanwhile, the dosage, plasmid level and concentration/dose ratio of tacrolimus were compared in the normotensive and hypertensive group.RESULTS: Hypertension was present in 104 post-transplantation patients out of 200 patients (52.0%). Spearman's correlation analysis revealed a positive correlation existed between systolic blood pressure (SBP) and the dose of tacrolimus (r=0.216, P＜0.05). However, there was no significant correlation between diastolic blood pressure and tacrolimus trough level.The oral dosage of tacrolimus in hypertension group (3.11±1.49) mg/d was higher than that in normotensive group (2.42±1.07) mg/d (P＜0.05). There was no significant difference in tacrolimus trough level between the two groups [HBP vs Nor: (7.76±3.86) ng/mL vs (7.56±2.67) ng/mL, P>0.05]. The concentration/dose ratio of tacrolimus was lower in hypertension group than that in normotensive group [(2.94±1.57) ng·d/mg·mL vs (3.95±3.02) ng·d/mg·mL, P＜0.05).CONCLUSION: The present study demonstrated that SBP of renal transplant patients was positively correlated with tacrolimus daily dosage. Administration of tacrolimus with higher dosage may increase the predisposition to hypertension.

Key words: Renal transplantation, Hypertension, Tacrolimus, Dose, Plasma concentration

中图分类号:

R544.1⁺4

席兰艳, 袁洪, 成柯, 朱利军, 阳国平, 张桂香, 黄志军. 移植后高血压与他克莫司剂量及血药浓度的关系[J]. 中国临床药理学与治疗学, 2012, 17(1): 78-82.

XI Lan-yan YUAN Hong, CHENG Ke, ZHU Li-jun, YANG Guo-ping, ZHANG Gui-xiang, HUANG Zhi-jun. Relationship between post-transplantation hypertension and dose, plasma concentration of tacrolimus[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(1): 78-82.

参考文献

[1] Opelz G, Wujciak T, Ritz E. Association of chronic kidney graft failure with recipient blood pressure. Collaborative Transplant Study [J].Kidney Int, 1998, 53(1): 217-222.
[2] Hohage H, Bruckner D, Arlt M, et al. Influence of cyclosporine A and FK506 on 24 h blood pressure monitoring in kidney transplant recipients [J].Clin Nephrol,1996,45(5):342-344.
[3] Pilecki T, Paczek L, Senatorski G, et al. Effect of immunosuppressive treatment on diurnal profile of blood pressure[J]. Pol Merkuriusz Lek,2002,13(Suppl 1):37-40.
[4] Gema FF, Emilio R, Rosalia V, et al. Traditional cardiovascular risk factors as clinical markers after kidney transplantation[J]. Transplant Rev, 2006, 20(2): 88-94.
[5] Nichelle L, Canet S, Garrigue V, et al. Arterial hypertension in renal transplant recipients treated with tacrolimus or cyclosporine-neoral[J].Transplant Proc, 2002, 34(7):2824-2825.
[6] Ligtenberg G, Hen RJ, Blankestijn PJ, et al. Cardiovascular risk factors in renal transplant patients: Cyclosporine A versus Tacrolimus[J].J Am Soc Nephrol, 2001, 12(2): 368-373.
[7] Ye F, Ying-Bin X, Yu-Guo W,et al. Roland hetzer tacrolimus versus cyclosporine microemulsion for heart transplant recipients: A Meta-analysis[J]. J Heart Lung Transplant, 2009, 28(1):58-66.
[8] 中国高血压防治指南委员会. 中国高血压防治指南(2005年修订版) [M].北京:人民卫生出版社,2006:26-27.
[9] Morales JM, Andres A, Rengel M, et al. Influence of cyclosporin, tacrolimus and rapamycin on renal function and arterial hypertension after renal transplantation[J]. Nephrol Dial Transplant, 2001,16( Suppl 1) :12.
[10] Kasiske BL, Ballantyne CM. Cardiovascular risk factors associated with immunosuppression in renal transplantation [J].Transplantation,2002,16(1):1-21.
[11] Hricik DE, Chareandee C, Knauss TC, et al. Hypertension after pancreas-kidney transplantation: role of bladder versus enteric pancreatic drainage [J].Transplantation, 2000, 70(3): 494-496.
[12] Hernández-Infante E, García-Martínez C, Beltrán-de-la-Luz S, et al. Prevalence of posttransplant hypertension in pediatric kidney transplant recipients: effect on long term allograft survival [J]. Rev Invest Clin, 2010, 62(5): 398-405.
[13] Carrasco FR, Pérez-Flores I, Calvo N, et al. Treatment of persistent hyperparathyroidism in renal transplant patients with cinacalcet improves control of blood pressure [J]. Transplant Proc, 2009,41(6): 2385-2387.
[14] Pirsch JD, Miller J, Deierhoi MH, et al. A comparison of tacrolimus (FK506) and Cyclosporine for immunosuppression after cadaveric renal transplantation [J].Transplantation, 1997, 63(7):977-983.
[15] Béji S, Abderrahim E, Kaaroud H,et al. Risk factors of arterial hypertension after renal transplantation[J]. Transplant Proc, 2007, 39(8): 2580-2582.
[16] Koomans HA, Ligtenberg G. Mechanisms and consequences of arterial hypertension after renal transplantation[J].Transplantation,2001,72(Suppl 6):S9.
[17] Bulatova N, Yousef AM, Al-Khayyat G, et al. Adverse effects of tacrolimus in renal transplant patients from living donors [J]. Curr Drug Saf, 2011,6(1):3-11.
[18] Takeda Y, Miyamori I, Furukawa K, et al. Mechanisms of FK506-induced hypertension in the rat [J]. Hypertension, 1999, 33(1): 130-136.
[19] De Lima JJ, Xue H, Coburn L, et al. Effects of FK506 in rat and human resistance arteries [J]. Kidney Int, 1999, 55(4): 1518-1527.
[20] 刘海, 戴秋艳, 彭志海, 等. 206例肝移植术后患者血压变化的观察[J].中华心血管病杂志, 2006, 34(10): 902-904.
[21] 朱琳, 华之卉, 宋洪涛. 他克莫司的药物基因组学与个体化用药[J]. 中国临床药理学与治疗学, 2011, 16( 6) : 710-715.
[22] Cai JJ, Huang ZJ, Yang GP, et al. Comparing antihypertensive effect and plasma cyclosporine a concentration between amlodipine and valsartan regimen in hypertensive renal transplant patients with cyclosporine a therapy[J]. Am J Cardiovasc Drugs, 2011,11(6):401-409.