Mycophenolate mofetil in islet cell transplant: Variable pharmacokinetics but good correlation between total and unbound concentrations
Mycophenolate mofetil in islet cell transplant: Variable pharmacokinetics but good correlation between total and unbound concentrations
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DOI：
10.1177/0091270005278599
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发表时间：
2005-08-01
影响因子：
2.9
通讯作者：
Hering, BJ
中科院分区：
文献类型：
--
作者：
Jacobson, PA;Green, KG;Hering, BJ
作者研究了8名接受胰岛细胞移植的高加索妇女1年内霉酚酸的药代动力学。60 d前总霉酚酸AUC(0 ~ 12) mcg中心点h/mL为62.1 ~ 67.8,60 d后下降至33.6 ~ 64.7 （P = 0.61）。中位总谷浓度为1.16-2.90微克/毫升。未结合AUC（0-12）为412-673 ng中心点h/mL，不随时间变化（P = 0.30）。未结合霉酚酸的中位数为总浓度的0.95%。个体未结合霉酚酸浓度与总霉酚酸浓度高度相关（r(2) = 0.94）。总霉酚酸谷浓度与总AUG（0 ~ 12）呈正相关（r(2) = 0.65）。全身霉酚酸暴露的患者内部和患者间变异性很高。6例患者由于不良反应需要在第60天之前减少剂量。所有受试者均实现胰岛素独立；3例术后移植物功能丧失。早期暴露量增加后剂量减少的趋势表明，降低初始剂量和治疗药物监测可能是必要的。
The authors investigated the pharmocokinetics of mycophenolic acid over 1 year in 8 Caucasian women undergoing islet cell transplantation. Total mycophenolic acid AUC(0-12) mcg center dot h/mL before day 60 was 62.1-67.8, declining to 33.6-64.7 thereafter (P = .61). Median total trough concentrations were 1.16-2.90 mcg/mL. Unbound AUC(0-12) was 412-673 ng center dot h/mL and did not change over time (P = .30). Median percent unbound mycophenolic acid was 0.95% of total concentrations. 1ndividual unbound and total mycophenolic acid concentrations were highly correlated (r(2) = 0.94). Total mycophenolic acid trough concentration and total AUG(0-12) were modestly correlated (r(2) = 0.65). Intra- and interpatient variability of systemic mycophenolic acid exposure was high. Six patients required dose reductions prior to day 60 due to adverse effects. All Subjects achieved insulin independence; 3 later lost graft function. The trend toward higher exposure in the early periods followed by, dose reductions suggests that lower Initial doses and therapeutic drug monitoring may be necessary.