CAJ | 학술논문

目的：探讨肝移植患者口服麦考酚钠肠溶片（ EC-MPS）后不同阶段霉酚酸（ MPA）及其代谢物的药动学特征。方法：采集24例肝移植患者服用EC-MPS后第1周和第3周0~12 h血标本，采用LC-MS/MS法测定MPA、7-O-葡萄糖醛酸结合代谢物（ MPAG）、酰化葡萄糖醛酸代谢物（ AcMPAG）等血浆中药物浓度，采用非房室法计算药动学参数。结果：服用EC-MPS1周与3周后，MPA的Cmax、AUC0-12、t1/2分别为（18.1±8.75）与（20.7 ± 16.0）μg·ml-1、（42.7 ± 17.5）与（47.1±23.9）μg·h ·ml-1、（3.33±2.81）与（3.30±1.89）h，其主要药动学参数在第1周与第3周无显著差异；AcMPAG的Cmax、AUC0-12、t1/2分别为（2.50±1.86）与（1.78±1.72）μg·ml-1、（14.5 ± 11.7）与（6.97±6.57）μg·h·ml-1、（4.48±2.53）与（3.76±1.89）h，给药后第1周AcMPAG的AUC0-12显著高于第3周（P<0.01）；MPAG的 Cmax、AUC0-12、t1/2分别为（171.6±135.4）与（152.2±115.9）μg·ml-1、（1299 ± 1204）与（1051±561）μg·h·ml-1、（8.73±4.25）与（7.75±2.87）h，其主要药动学参数在第1周与第3周无显著差异。服用吗替麦考酚酯（MMF）与EC-MPS患者的MPA的Cmax、Tmax、t1/2存在显著差异（P<0.05）；治疗3周后代谢物MPAG的Cmax、AUC0-12显著高于服用MMF的患者（P<0.05）。结论：不同阶段MPA蓄积不明显，但代谢物体内暴露差异明显。与服用MMF的患者相比，EC-MPS吸收延缓，而体内暴露无差异。
목적：탐토간이식환자구복맥고분납장용편（ EC-MPS）후불동계단매분산（ MPA）급기대사물적약동학특정。방법：채집24례간이식환자복용EC-MPS후제1주화제3주0~12 h혈표본，채용LC-MS/MS법측정MPA、7-O-포도당철산결합대사물（ MPAG）、선화포도당철산대사물（ AcMPAG）등혈장중약물농도，채용비방실법계산약동학삼수。결과：복용EC-MPS1주여3주후，MPA적Cmax、AUC0-12、t1/2분별위（18.1±8.75）여（20.7 ± 16.0）μg·ml-1、（42.7 ± 17.5）여（47.1±23.9）μg·h ·ml-1、（3.33±2.81）여（3.30±1.89）h，기주요약동학삼수재제1주여제3주무현저차이；AcMPAG적Cmax、AUC0-12、t1/2분별위（2.50±1.86）여（1.78±1.72）μg·ml-1、（14.5 ± 11.7）여（6.97±6.57）μg·h·ml-1、（4.48±2.53）여（3.76±1.89）h，급약후제1주AcMPAG적AUC0-12현저고우제3주（P<0.01）；MPAG적 Cmax、AUC0-12、t1/2분별위（171.6±135.4）여（152.2±115.9）μg·ml-1、（1299 ± 1204）여（1051±561）μg·h·ml-1、（8.73±4.25）여（7.75±2.87）h，기주요약동학삼수재제1주여제3주무현저차이。복용마체맥고분지（MMF）여EC-MPS환자적MPA적Cmax、Tmax、t1/2존재현저차이（P<0.05）；치료3주후대사물MPAG적Cmax、AUC0-12현저고우복용MMF적환자（P<0.05）。결론：불동계단MPA축적불명현，단대사물체내폭로차이명현。여복용MMF적환자상비，EC-MPS흡수연완，이체내폭로무차이。
Objective:To investigate the pharmacokinetics of mycophenolic acid( MPA)and its metabolites in different stages af-ter the administration of enteric-coated mycophenolate sodium( EC-MPS)tablets in Chinese liver transplant recipients. Methods:The blood samples of 24 patients were collected in 0-12h of the 1st and 3rd week after the administration of EC-MPS. The concentrations of MPA,AcMPAG and MPAG in plasma were measured by LC-MS/MS developed in our lab. The pharmacokinetic parameters of MPA and its metabolites were estimated by non-compartmental method. Results:After 1-and 3-week therapy with EC-MPS,Cmax ,AUC0-12 and t1/2 was(18. 1 ± 8. 75)and(20. 7 ± 16. 0)μg ml-1 ,(42. 7 ± 17. 5)and(47. 1 ± 23. 9)μg·h·ml-1 ,(3. 33 ± 2. 81)and (3.30 ±1.89)h for MPA;(2.50 ±1.86)and(1.78 ±1.72)μg·ml-1,(14.5 ±11.7)and(6.97 ±6.57)μg·h·ml-1, (4. 48 ± 2. 53)and(3. 76 ± 1. 8)h for AcMPAG;(171. 6 ± 135. 4)and(152. 2 ± 115. 9)μg·ml-1 ,(1299 ± 1 204)and(1 051 ± 561)μg·h·ml-1 ,(8. 73 ± 4. 25)and(7. 75 ± 2. 87)h for MPAG,respectively. There was no significant difference in the PK parameters of MPA after the 1-and 3-week therapy. The Cmax ,Tmax and t1/2 of MPA in the patients received EC-MPS were significantly higher than those in the patients received MMF(P<0. 05). Cmax and AUC0-12 of MPAG in the patients received EC-MPS were signifi-cantly higher than those in the patients received MMF after the 3-week therapy(P<0. 05). Conclusion:There is no significant accu-mulation of MPA after the therapy with EC-MPS at different stages. The absorption of MPA is delayed after the therapy with EC-MPS compared with that with MMF. There is no difference in MPA exposure between EC-MPS and MMF in Chinese liver transplant patients.