霉酚酸对肝移植受者外周血单核细胞IMPDH活性的影响

Effects of Mycophenolic Acid on IMPDH Activity in Peripheral Blood Mononuclear Cells in Liver Transplant Patients

关键词:  次黄嘌呤核苷酸脱氢酶  霉酚酸酯  霉酚酸  肝移植

Key words:  inosine monophosphate dehydrogenase  mycophenolate mofetil  mycophenolic acid  liver transplantation

摘要:

目的 探讨中国肝移植受者术后早期外周血单核细胞次黄嘌呤核苷酸脱氢酶(IMPDH)活性变化与血浆霉酚酸(MPA)浓度变化之间的相关性。方法 22例肝移植受者术后应用他克莫司、霉酚酸酯(MMF)和糖皮质激素三联免疫抑制方案。移植后早期采集口服MMF前及服药后0.5，1，1.5，2，4，6，8，10，12 h外周血，检测MPA血药浓度，同时测定口服MMF前及后1，2 h外周血单核细胞IMPDH活性。结果 肝移植受者外周血单核细胞IMPDH活性存在个体间差异，与血浆MPA浓度之间呈显著负相关(P<0.05)。与服药前相比，服药后1 h IMPDH活性显著下降(P<0.05)。结论 肝移植受者口服MMF后外周血单核细胞IMPDH活性显著下降，可以作为MPA药效学监测指标。

Abstract:

OBJECTIVE To determine the relationship between mycophenolic acid (MPA) concentrations and inosine monophosphate dehydrogenase (IMPDH) activity in peripheral blood mononuclear cells (PBMC) in liver transplant patients. METHODS Twenty-two liver transplant patients received mycophenolate mofetil (MMF) in combination with tacrolimus and steroids were enrolled. For investigating MPA pharmacokinetic profile, plasma MPA concentrations was monitored before MMF dosing and at 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12 h after MMF dosing during the early period after transplantation, and the IMPDH activity on mononuclear cells was measured before dosing and at 1, 2 h after dosing. RESULTS A high inter-individual variability in IMPDH activity was observed. The values of IMPDH activity were inversely related to plasma MPA concentrations (P<0.05). IMPDH activity changed inversely with MPA concentration before dosing and 2 hours after dosing. The values of IMPDH activity at 1 h after dosing were significantly lower than the pre-dose values (P<0.05). CONCLUSION IMPDH activity was reduced significantly with MMF therapy in liver transplant recipients, which may be a surrogate pharmacodynamics marker of MPA-induced immunosuppression.