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| 中国肝移植患者服用麦考酚钠肠溶片后霉酚酸及其代谢物的药动学研究 |
| Pharmacokinetics of Mycophenolic Acid and its Metabolites in Chinese Liver Transplant Patients after Administration of Enteric coated Mycophenolate Sodium (EC-MPS) Tablets |
| 投稿时间：2014-10-29 修订日期：2014-12-28 |
| DOI： |
| 中文关键词: 麦考酚钠肠溶片 肝移植 药动学 霉酚酸 7-O-葡萄糖醛酸结合代谢物 酰化葡萄糖醛酸代谢物 |
| 英文关键词:Enteric coated mycophenolate sodium tablets Liver transplantation Pharmacokinetics Mycophenolic acid 7-O-Glucuronide conjugate of MPA Acyl glucuronide of MPA |
| 基金项目:国家自然科学基金项目(编号：81473275)；上海市自然科学基金项目(编号：12ZR1418900) |
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| 中文摘要: |
| 摘 要 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、（1 299±1 204）与（1 051±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。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the pharmacokinetics of mycophenolic acid (MPA) and its metabolites in different stages after 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 AUC0-12of MPAG in the patients received EC-MPS were significantly higher than those in the patients received MMF after the 3 week therapy (P<0.05). Conclusion:There is no significant accumulation 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. |
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