摘要
目的 本试验旨在考察我院肾移植患者术后早期应用质子泵抑制剂（PPIs）和后期停用PPIs后对霉酚酸酯(MMF)谷浓度的影响。方法 选择2009年～2010年在我院接受同种异体活体肾移植术的患者进行研究，所有患者均采用他克莫司（FK506）+霉酚酸酯（MMF）+泼尼松(Pred)的三联用药方案。利用HPLC法检测血浆霉酚酸（MPA）浓度，结合临床检验结果分析PPIs对MMF的影响。结果 术后早期服用PPIs的患者MPA谷浓度为（2.58±2.63）μg·mL-1，停用PPIs后MPA浓度为（1.98±1.57）μg·mL-1，二者无统计学差异。结论 移植早期应用PPIs不会降低MPA谷浓度，MMF固定剂量给药可使MPA浓度维持在目标浓度范围内。
Abstract
OBJECTIVE To explore the impact of PPIs therapy on mycophenolate mofetil（MMF） trough concentration in renal transplant recipients. METHODS Patients were enrolled after receiving de novo kidney transplantation in 2009-2010. The pharmacotherapy regimen was tacrolimus、mycophenolate mofiteil and prednisone. The concentration of mycophenolic acid in plasma was detected with HPLC. RESULTS The trough concentration of MPA in the patients using PPIs after kidney transplantation was 2.58±2.63μg·mL-1， and that in the patients after withdrawing PPIs was （1.98±1.57）μg·mL-1. There was no significance difference between these two groups. The clinical relevance between MPA trough concentration and creatinine or urea was minor. CONCLUSION Compared with the group without PPIs， PPIs therapy in combination with MMF does not appear to have a significant impact on early MPA trough concentration. The strategy of fixed dose of MMF can generate adequate concentration in patients whether or not receiving PPIs therapy.
关键词
肾移植 /
治疗药物监测 /
霉酚酸酯 /
质子泵抑制剂
{{custom_keyword}} /
Key words
renal transplant /
therapeutic drug monitoring /
mycophenolate mofetil(MMF) /
proton pump inhibitors(PPIs)
{{custom_keyword}} /
贾自力 赵莉 车慧 刘晓 李朋梅 刘峻瑒 张镭 张相林.
质子泵抑制剂对肾移植患者体内霉酚酸酯血药浓度的影响[J]. 中国药学杂志, 2011, 46(16): 1273-1275
JI Zi-li;ZHO Li;CHE Hui;LIU Xio;LI Peng-mei;LIU Jun-yng;ZHNG Lei;ZHNG Xing-lin.
Effects of proton pump inhibitors on mycophenolate trough concentration in renal transplant recipients[J]. Chinese Pharmaceutical Journal, 2011, 46(16): 1273-1275
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] LI P M， ZHANG X L， TANG K， et al. Determination of mycophcnolic acid concentration in human plasma and its application to therapeutic drug monitoring in renal transplantation patient[J]. Chin Pharm J(中国药学杂志)，2007，42(19)：1490-1493.
[2] TROPPMANN C， PAPALOIS B E， CHIOU A， et al. Incidence， complications， treatment， and outcome of ulcers of the upper gastrointestinal tract after renal transplantation during the cyclosporine era[J]. J Am Coll Surg， 1995， 180(4)：433-443.
[3] CHEN K J， CHEN C H， CHENG C H， et al. Risk factors for peptic ulcer disease in renal transplant patient-11 years of experience from a single center[J]. Clin Nephrol， 2004，62(1)：14-20.
[4] SUWELACK B， GABRIELS G， VOLMER S， et al. Resolution of severe MMF related gastrointestinal adverse events following conversion to entericcoated mycophenolate sodium[J]. Transplantation， 2005，79(8)：987-988.
[5] ALTOMARE J F， SMITH R E， POTDAR S， et al. Delayed gastric ulcer healing associated with sirolimus[J]. Transplantation， 2006， 82(3)：437-438.
[6] STAATZ C E， TETT S E. Clinical pharmacokinetics and pharmacodynamics of mycophenolate in solid organ transplant recipients[J]. Clin Pharmacokinet， 2007， 46(1)：13-58.
[7] KIBERD BA， WROBEL M， DANDAVINO R， et al. The role of proton pump inhibitors on early mycophenolic acid exposure in kidney transplantation： evidence from the CLEAR study[J]. Ther Drug Monit， 2011 Feb;33(1)：120-123.
[8] BULLINGHAM R， SHAH J， GOLDBLUM R， et al. Effects of food and antacid on the pharmacokinetics of single doses of mycophenolate mofetil in rheumatoid arthritis patients[J]. Br J Clin Pharmacol， 1996，41(6)：513-516.
[9] KOFLER S， DEUTSCH M-A， BIGDELI AK， et al. Proton pump inhibitor co-medication reduces mycophenolate acid drug exposure in heart transplant recipients[J]. J Heart Lung Transplant，2009，28(6)：605-611.
[10] KOFLER S， SHVETS N， BIGDELI AK， et al. Proton pump inhibitors reduce mycophenolate exposure in heart transplant recipients—a prospective case-controlled study[J]. Am J Transplant，2009，9(7)：1650-1656.
[11] RUPPRECHT K， SCHMIDT C， RASPE′ A， et al. Bioavailability of mycophenolate mofetil and enteric-coated mycophenolate sodium is differentially affected by pantoprazole in healthy volunteers[J]. J Clin Pharmacol，2009，49(10)：1196-1201.
[12] MIURA M， SATOH S， INOUE K， et al. Influence of lansoprazole and rabeprazole on mycophenolic acid pharmacokinetics one year after renal transplantation[J]. Ther Drug Monit，2008，30(1)：46-51.
[13] SCHAIER M， SCHOLL C， SCHARPF D， et al. Proton pump inhibitors interfere with the immunosuppressive potency of mycophenolate mofetil[J]. Rheumatology， 2010，49(11)：2061-2067.
[14] VAN GELDER T， PESCOVITZ M， ELZEIN H， et al. The effect of gastric pH modulators on the pharmacokinetics of mycophenolate mofetil (MMF) in de novo renal transplant patients[J]. Presented at the International Congress of the Transplantation Society 2004 [Abstract].
[15] FAN P Y W， BARRACLOUGH K A， ISBEL N M， et al. Impact of omeprazole on mycophenolic acid pharmacokinetics in adult kidney transplant recipients[J]. Presented at the International Congress of the Transplantation Society， 2010 [Abstract].
[16] POOMMIPANIT N B， BUNNAPRADIST S. CNI sparing： short-term results promising， but long-term data needed[J]. Nephrology times， 2009，2(8)：6-10.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
PDF(656 KB)
