中国临床药学杂志2025，Vol.34Issue(6)：401-407,7.DOI:10.19577/j.1007-4406.2025.06.001
肾移植患者外周血单个核细胞内霉酚酸暴露量与次黄嘌呤单核苷酸脱氢酶活性的相关性研究
Relationship between pharmacokinetics and IMPDH activity in PBMC after mycophenolic acid administration in renal transplant patients
摘要
Abstract
AIM To study the pharmacokinetics of mycophenolic acid(MPA)in peripheral blood mononuclear cell(PBMC),and the correlation with inosine-5'-monophosphate dehydrogenase(IMPDH)activity in renal transplantation patients.METHODS A total of 48 renal transplant patients were included and divided into mycophenolate mofetil(MMF)group and enteric-coated mycophenolate sodium tablets(EC-MPS)group according to different MPA formulation types,with 24 patients in each group.Plasma samples were collected at baseline(0 h)and 0.5,1.0,1.5,2.0,4.0,6.0,8.0,10.0,and 12.0 hours after the administration of MMF or EC-MPS over 2 weeks from renal transplant patients.MPA concentration and xanthosine monophosphate(XMP)concentration(for calculation of IMPDH activity)in plasma and PBMC were measured by liquid chromatography-tandem mass spectrometry(LC-MS/MS).Pearson method was used to analyze the correlation between pharmacokinetic parameters of MPA in PBMC(mainly C0,Cmax and AUC0-12h related to exposure)and plasma,as well as the correlation between IMPDH activity and MPA concentration in plasma and PBMC.RESULTS For renal transplant recipients administered MMF or EC-MPS,the time to peak concentration of MPA in PBMC was consistent with that in plasma.There were statistically significant positive correlations between plasma and PBMC for Cmax(r=0.538,P＜0.01),C0(r=0.503,P＜0.05),and AUC0-12h(r=0.472,P＜0.05)in patients taking MMF.The correlation coefficients for patients receiving EC-MPS were as follows:r=0.147(P=0.494)for Cmax,r=0.315(P=0.143)for C0,and r=0.431(P=0.065)for AUC0-12h.The activity of IMPDH decreased in an inverse relationship with increasing MPA concentrations in transplanted patients following drug administration,and the trend was more remarkable in PBMC.CONCLUSION A correlation between MPA exposure levels in PBMC and those in plasma has been observed.The MPA concentration in PBMC has been shown to reflect the inhibitory effect of MPA on IMPDH activity directly.Consequently,the MPA concentration in PBMC can be utilized as a complement to the TDM.关键词
霉酚酸/次黄嘌呤单核苷酸脱氢酶/外周血单个核细胞/药动学Key words
mycophenolic acid/inosine-5'-monophosphate dehydrogenase/peripheral blood mononuclear cell/pharmacokinetics分类
医药卫生引用本文复制引用
陆韵竹,陆佳倩,邵琨,王雨萍,安会敏,石浩强,周佩军,陈冰..肾移植患者外周血单个核细胞内霉酚酸暴露量与次黄嘌呤单核苷酸脱氢酶活性的相关性研究[J].中国临床药学杂志,2025,34(6):401-407,7.基金项目
国家自然科学基金(编号81973387) （编号81973387）
