麦考酚酸在早期肾移植患者中的药动学研究  

Pharmacokinetics Study of Mycophenolic Acid in Early Renal Transplant Patients

作　　者：罗永刚[1] 朱振峰[2] 孙志[2] 李卓伦 师莹莹 刘丽伟 张俊[2] 张晓坚[2] LUO Yong-gang;ZHU Zhen-feng;SUN Zhi;LI Zhuo-lun;SHI Ying-ying;LIU Li-wei;ZHANG Jun;ZHANG Xiao-jian(The First Affiliated Hospital of Zhengzhou University,a.Department of Integrated Intensive Care Uni;b.Department of Pharmacy,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院综合ICU,郑州450052 [2]郑州大学第一附属医院药学部,郑州450052

出　　处：《中国药学杂志》2018年第18期1589-1593,共5页Chinese Pharmaceutical Journal

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)

摘　　要：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:AUC_(0-12 h)分别为(43.62±16.20)和(42.02±14.40)mg·h·L^(-1)(P>0.05);ρ_(max)分别为(17.85±11.32)和(13.96±5.11)mg·L^(-1)(P>0.05);t_(max)分别为(2.72±1.74)和(1.32±0.42)h(P<0.05);ρ_0分别为(1.63±1.18)和(1.66±0.93)mg·L^(-1)(P>0.05);ρ_(12)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。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 rag, ql2h）, 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： AU0-12h were（43.62±16. 20） and（42. 02±14.40） mg·L^-1（ P 〉 0. 05 ） ;pmax 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）;p0 were（1.63±1. 18） and（1.66±0.93） mg·L^-1（P〉0.05）;p12 were（1.84±2.09） and（1.81±l.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 

分 类 号：R969.1[医药卫生—药理学]