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

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.