
肾移植患者术后免疫抑制治疗中的吗替麦考酚酯药物暴露分析
Analysis of Mycophenolate Mofetil Exposure in Kidney Transplant Patients Receiving Immunosuppressive Therapy
目的 分析肾移植患者术后免疫抑制治疗的吗替麦考酚酯药物暴露个体体征,评价开展治疗药物监测必要性。方法 纳入97例肾移植术后免疫抑制治疗患者,分析霉酚酸血浆浓度谷值为药物暴露标志的特征,参考国内外推荐治疗药物暴露靶值1~3.5 μg·mL-1,评估个体化治疗必要性。统计分析运用SPSS20.0,就监测数据状态做正态分布图,采用完全随机设计的单因素方差分析不同条件下的监测结果。结果 监测总样本及不同因素下样本的霉酚酸暴露数据状态符合正态分布,总样本计526例次的血药浓度(2.51±1.79)μg·mL-1,其中332例次达到推荐靶值范围,平均血药浓度为(2.08±0.71)μg·mL-1,达标率为63.0%。不同因素下状态比较:男女两组间血药浓度无统计学差异(P>0.05);中青年(18~64岁)组和老年(65~77岁)组间血药浓度有统计学差异(P<0.05);不同给药剂量组两两进行比较,血药浓度无统计学差异(P>0.05)。不同给药方案的影响, MMF+CsA+Pre和MMF+FK506+Pre组、MMF+CsA组和MMF+FK506组、MMF+FK506+Pre组和MMF+CsA组、MMF+CsA+Pre组和MMF+FK506组分别对比,血药浓度有统计学差异(P<0.05)。结论 吗替麦考酚酯临床治疗个体差异较大,影响药物暴露的因素涉及年龄、剂量和合并用药等,有必要实施治疗药物监测,进行个体化治疗。
OBJECTIVE To analyze the individual features of mycophenolate mofetil exposure in renal transplantation patients receiving immunosuppressive therapy postoperatively to provide reference for clinical individualized medication.METHODS Ninety-seven cases of renal transplantation patients were included in the study, with mycophenolic acid blood concentrations determined by HPLC method. The mycophenolic acid exposure characteristics was analyzed,using the domestic and foreign recommended drug exposure target value of 30-60 μg·h·mL-1 as reference. SPSS20.0 was used to analyze the data.Normal distribution diagram was drawn for the data and single factor analysis of variance with a completely randomized design was performed to compare the drug exposures under different conditions.RESULTS The study included 526 cases of mycophenolic acid plasma concentration data. The trough concentration was (2.51±1.79) μg·mL-1, and 332 cases reached the recommended plasma concentration range. The average plasma concentration was (2.08±0.71) μg·mL-1, and the target achievement rate was 63.0%. There was no significant difference in the plasma concentrations between male and female patients (P>0.05). The plasma concentrations were significantly different between middle-aged (18-64 y) and elderly (65 to 77 y) patients (P<0.05). There was no significant difference in the plasma concentrations among different dosage groups (P>0.05). Between the different treatment groups, ie MMF+CsA+Pre group and MMF+FK506+Pre group (P=0.00), MMF+CsA group and MMF+FK506 group (P=0.00), MMF+FK506+Pre group and MMF+CsA group (P=0.00), MMF+CsA+Pre group and MMF+FK506 group (P=0.00), the plasma concentrations were significantly different (P<0.05). There was no statistically significant difference in the plasma drug concentrations among patients with different GFRs (P>0.05).CONCLUSION There is remarkable inter-individual difference in the plasma concentration of mycophenolic acid, and a variety of clinical factors affect the drug exposure. Therefore, it is necessary to carry out therapeutic drug monitoring for mycophenolic acid in order to lay the foundation for individualized treatment.
吗替麦考酚酯 / 治疗药物监测 / 药物暴露 {{custom_keyword}} /
mycophenolic acid / therapeutic drug monitoring / drug exposure {{custom_keyword}} /
[1] KNIGHT S R, MORRIS P J. Does the evidence support the use ofmycophenolate mofetil therapeutic drug monitoring inclinical practice? A systematic review [J].Transplantation,2008,85:1675-1685.
[2] KUYPERS D R, LE M Y, CANTAROVICH M, et al. Consensus report on therapeutic drug monitoring of mycophenolic acid in solid organ transplantation [J]. Clin J Am Soc Nephrol, 2010, 5(2):341-358.
[3] ARNS W, CIBRIK D M, WALKER R G, et al. Therapeutic drug monitoring of mycophenolic acid in solid organ transplant patients treated with mycophenolate mofetil: review of the literature [J]. Transplantation, 2006, 82(8):1004-1012.
[4] COX V C, ENSOM M H. Mycophenolate mofetil for solid organ transplantation: does the evidence support the need for clinical pharmacokinetic monitoring?[J]. Ther Drug Monit, 2003, 25(2):137-157.
[5] VAN GELDER T, LE M Y, SHAW L M, et al. Therapeutic drug monitoring of mycophenolate mofetil in transplantation[J]. Ther Drug Monit, 2006, 28(2):145-154.
[6] LI P M, ZHANG X L, TANG K, et al. Measurement method research and drug monitoring application of mycophenolic acid in human plasma concentration [J]. Chin Pharm J(中国药学杂志),2007,42(19):1490-1493.
[7] MATHEW B S, FLEMING D H, ANNAPANDIAN V M, et al. A reliable limited sampling strategy for the estimation of mycophenolic acid area under the concentration time curve in adult renal transplant patients in the stable posttransplant period[J]. Ther Drug Monit,2010,32(2):136-140.
[8] SHAW L M, HOLT D W, OELLERICH M, et al. Current issuesinless, the identified relationships may help to apply therapeutic drug monitoring of mycophenolic acid:report of around table discussion [J]. Ther Drug Monit, 2001, 23:305-315.
[9] JEONG H, KAPLAN B. Therapeutic monitoring of mycophenolate mofetil [J]. Clin J Am Soc Nephrol, 2007, 2(1):184-191.
[10] PAWINSKI T,DURLIK M,SZLASKA I,et al. Comparison of mycophenolic acid pharmacokinetic parameters in kidney transplant patients within the first 3 months post-transplant[J]. J Clin Pharm Ther,2006,31(1):27-34.
[11] SWEETMAN, MARTINDALE S C. The Complete Drug Reference[M]. Beijing:Chemical Industry Press, 2013:1752.
[12] PESCOVITZ M D, ANTONIO G, ROBERT G, et al. Equivalent pharmacokinetics of mycophenolate mofetil in African-American and Caucasian male and female stable renal allograft recipients [J]. Am J Transplant, 2003, 3(12):1581-1586.
[13] HEST R M V, GELDER T V, VULTO A G, et al. Population pharmacokinetics of mycophenolic acid in renal transplant recipients [J].Clin Pharmacokinet, 2005, 44(10):1083-1096.
[14] ZUCKER K, ROSEN A, TSAROUCHA A, et al. Unexpected augmentation of mycophenolic acid pharmacokinetics in renal transplant patients receiving tacrolimus and mycophenolate mofetil in combination therapy, and analogous in vitro findings[J].Transpl Immunol, 1997, 5(3):225-232.
[15] HEST R M V, MATHOT R A A, PESCOVITZ M D, et al. Explaining variability in mycophenolic acid exposure to optimize mycophenolate mofetil dosing: a population pharmacokinetic meta-analysis of mycophenolic acid in renal transplant recipients[J]. J Am Soc Nephrol, 2006, 17(3):871-880.
[16] GREGOOR P J, HESSE C J, VOS P, et al. Effect of cyclosporine on mycophenolic acid trough levels in kidney transplant recipients[J]. Transplantation, 1999, 68(10):1603-1606.
[17] SHIPKOVA M , ARMSTRONG V W, KUYPEERS D,et al. Effect of cyclosporine withdrawal on mycophenolic acid pharmacokinetics in kidney transplant recipients with deteriorating renal function: preliminary report[J]. Ther Drug Monit, 2002, 23(6):717-721.
[18] VAN G T, SMAK GREGOOR P J, WEIMAR W. Drug interaction between mycophenolate mofetil and tacrolimus detectable within therapeutic mycophenolic acid monitoring in renal transplant patients[J]. Ther Drug Monit, 1999, 21(5):536-539.
[19] HÜBNER G I, EISMANN R ,SZIEGOLEIT W. Drug interaction between mycophenolate mofetil and tacrolimus detectable within therapeutic mycophenolic acid monitoring in renal transplant patients[J]. Ther Drug Monit, 2000, 21(5):536-539.
[20] LIU J Y, CUI G, ZHAO L, et al. Assessment of mycophenolic acid exposure in clinic practice [J]. Drugs Eval(药品评价), 2012(23):28-32.
[21] PESCOVITZ M D, GUASCH A, GASTON R, et al. Equivalent pharmacokinetics of mycophenolate Mofetil in African-American and Caucasian Male and Female Stable Renal Allograft Recipients[J]. Am J Transplant, 2003, 3(12):1581-1586.
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