目的 比较多次口服麦考酚钠肠溶片(EC-MPS)或吗替麦考酚酯(MMF)分散片在早期肾移植患者体内的药动学特点,为临床合理用药提供参考依据。方法 选取38例首次进行肾移植患者,随机分为2组,分别连续服用EC-MPS或MMF分散片联合他克莫司和甲泼尼龙预防急性排斥反应,于术后第5天服药前(0 h)及服药后0.5,1,1.5,2,3,4,6,8,10,12 h采集静脉血2 mL,麦考酚酸(MPA)血浆浓度采用酶放大免疫法测定,得出2种剂型的主要药动学参数。结果 EC-MPS和MMF分散片的主要药动学参数:AUC0-12 h分别为(43.62±16.20)和(42.02±14.40)mg·h·L-1(P>0.05);ρmax分别为(17.85±11.32)和 (13.96±5.11) mg·L-1(P>0.05);tmax分别为(2.72±1.74)和(1.32±0.42)h(P<0.05);ρ0分别为(1.63±1.18)和(1.66±0.93)mg·L-1(P>0.05);ρ12分别为(1.84±2.09)和(1.81±1.76) mg·L-1(P>0.05);CL分别为(14.12±5.30)和 (19.66±5.99)L·h-1 (P<0.05)。2组大部分患者均在给药后4~12 h出现第2个小峰。结论 EC-MPS和MMF分散片在早期肾移植患者体内的药动学参数个体间变异大,均需要参考血药浓度监测结果调整用药剂量。
Abstract
OBJECTIVE To investigate the pharmacokinetic characteristics of enteric-coated sodium mycophenolate(EC-MPS) or mycophenolate mofetil (MMF) dispersible tablets after multiple oral doses in early renal transplant patients, providing references for the rational use of the study drugs in clinical practice. METHODS Thirty-eight first-time renal transplant patients were selected and randomly divided into EC-MPS group (n=18) or MMF dispersible tablets group (n=19). The patients received EC-MPS (540 mg, q12h) or MMF dispersible tablets (750 mg, q12h), combined with tacrolimus and methylprednisolone to prevent acute rejection, respectively. Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 h after oral administration on the postoperative day 5. Enzyme multiplied immunoassay technique (EMIT) was employed to determine the plasma concentration of MPA. The main pharmacokinetic parameters of the two durgs were assessed. RESULTS Pharmacokinetic parameters on the postoperative day 5 of EC-MPS and MMF dispersible tablet were as follows: AUC0-12 h were(43.62±16.20) and(42.02±14.40)mg·h·L-1(P>0.05);ρmax were (17.85±11.32) and (13.96±5.11) mg·L-1(P>0.05);tmax were (2.72±1.74) and(1.32±0.42)h(P<0.05); ρ0 were (1.63±1.18) and (1.66±0.93) mg·L-1(P>0.05); ρ12 were(1.84±2.09) and (1.81±1.76) mg·L-1(P>0.05); CL were (14.12±5.30) and (19.66±5.99) L·h-1(P<0.05). Most of the patients revealed a second small peak in the 4-12 h after taking MPA in the two study groups. CONCLUSION There are large individual differences of pharmacokinetic between EC-MPS and MMF dispersible tablets in early renal transplant patients. It is necessary to carry out therapeutic drug monitoring of MPA to guide the adjustment of drug dosage.
关键词
麦考酚钠肠溶片 /
吗替麦考酚酯分散片 /
麦考酚酸 /
药动学 /
肾移植
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Key words
EC-MPS /
MMF dispersible tablet /
MPA /
pharmacokinetics /
renal transplantation
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中图分类号：
R969.1
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参考文献
[1] PELLETIER R P, AKIN B, HENRY M L, et al. The impact of mycophenolate mofetil dosing patterns on outcomes in renal transplantation . Clin Transplant,2003, 17(3):200-205.
[2] SÁNCHEZ FRUCTUOSO A,CALVO N,MORENO M A,et al. Better mycophenolic acid 12-hour trough level after enteric-coated mycophenolate sodium in patients with gastrointestinal intolerance to mycophenolate mofetil . Transplant Proc, 2007, 39(7): 2194-2196.
[3] VAN GELDER T, HILBRANDS L B, VANRENTERGHEM Y, et al. A randomized double-blind,multicenter plasma concentration controlled study of the safety and efficacy of oral mycophenolate mofetil for the prevention of acute rejection after kidney transplantation . Transplantation, 1999, 68(2):261-266.
[4] WEBER L T, SHIPKOVA M, ARMSTRONG V W, et al. Comparison of the emit immunoassay with hplc for therapeutic drug monitoring of mycophenolic acid in pediatric renal-transplant recipients on mycophenolate mofetil therapy. Clin Chem, 2002, 48(3):517-525.
[5] YAO X L, HUANG H, WEI C, et al. Limited sampling strategy for mycophenolic acid in Chinese kidney transplant recipients receiving enteric-coated mycophenolate sodium and tacrolimus during the early posttransplantation phase. Ther Drug Monit, 2015, 37(4):516-523.
[6] ZHANG J, JIA M M, ZUO L H, et al. Nonlinear relationship between enteric-coated mycophenolate sodium dose and mycophenolic acid exposure in Han kidney transplantation recipients. Acta Pharm Sin B(药学学报英文版), 2017, 7(3):347-352.
[7] DE WINTER B C, MATHOT R A, SOMBOGAARD F, et al. Nonlinear relationship between mycophenolatemofetil dose and mycophenolic acid exposure: implications for therapeutic drug monitoring. Clin J Am Soc Nephrol, 2011, 6(3):656-663.
[8] STAATZ C E,TETT S E. Clinical pharmacokinetics and pharmacodynamics of mycophenolate in solid organ transplant recipients . Clin Pharmacol, 2007, 46(1):13-58.
[9] ARNS W,BREUER S,CHOUDHURY S,et al. Enteric-coated mycophenolate sodium delivers bioequivalent MPA exposure compared with mycophenolate mofetil . Clin Transplant,2005, 19(2):199-206.
[10] YU Z C, ZHOU P J, WANG X H, et al. Population pharmacokinetics and Bayesian estimation of mycophenolic acid concentrations in Chinese adult renal transplant recipients. Acta Pharmacol Sin(中国药理学报), 2017, 38(11): 1566-1579.
[11] JEONG H, KAPLAN B. Therapeutic monitoring of mycophenolate mofetil. Clin J Am Soc Nephrol,2007, 2(1): 184-191.
[12] 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. Transplant,2006, 82(8):1004-1012.
[13] ZHANG J, JIA M M, ZUO L H, et al. Pharmacokinetics study of mycophenolate mofetil dispersible tablets in early renal transplant patients. Chin Pharm J(中国药学杂志),2017, 52(8):666-670.
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脚注
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基金
河南省医学科技攻关计划项目资助(201702044);河南省卫计委普通项目资助(201602011);河南省重点研发与推广专项项目(182300410354)
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