Department of Pharmacy, Akita University Hospital, and Department of Urology, Akita University School of Medicine, Akita, Japan.
Ther Drug Monit. 2011 Jun;33(3):295-302. doi: 10.1097/FTD.0b013e3182197e38.
Routine therapeutic drug monitoring of mycophenolic acid (MPA) is generally performed using the area under the concentration-time curve from 0 to 12 hours (AUC0-12) with recommended values between 30 and 60 μg·h/mL.
The aim of this study was to examine whether the monitoring of the MPA predose concentration (C0) in patients who are stable for >1 year after renal transplantation was practical and to determine factors that cause MPA C0 variability among patients.
Eighty-six Japanese patients who had undergone renal transplantation and were taking tacrolimus and who had their MPA C0 analyzed >6 times by high-performance liquid chromatography for >1 year posttransplantation were enrolled.
Recipients with MPA AUC0-12 levels<30 μg·h/mL on day 28 and 1 year after transplantation had an MPA C0 of <2.0 μg/mL, with a sensitivity of 90.9% and a specificity of 70.7%. There was no significant difference in the mean dose-adjusted MPA C0>1 year after transplantation between subjects with either the UGT (1A1, 1A9, and 2B7) or drug transporter (SLCO1B3, ABCC2, and ABCG2) genotypes. However, in a multiple regression analysis, the dose-adjusted mean MPA C0>1 year after transplantation was significantly associated with age (P=0.0035), creatinine clearance (P=0.0001), and the dose-adjusted MPA AUC0-12 at 1 year (P=0.0147).
To keep the MPA AUC0-12>30 μg·h/mL, the plasma threshold for maintaining the MPA C0 with tacrolimus should be set >2.0 μg/mL as determined by high-performance liquid chromatography. For patients who are stable for >1 year after transplantation, continued monitoring of the MPA C0 using the same samples used to monitor the tacrolimus C0 and the additional assessment of the MPA AUC0-12 at the 1-year time point seem to be a viable option. If a change of the mycophenolate mofetil dose seems necessary based on the routine MPA C0 information, the determination of MPA AUC0-12 using a limited sampling strategy is recommended.
通常使用 0 至 12 小时的浓度-时间曲线下面积（AUC0-12）来对霉酚酸（MPA）进行常规治疗药物监测，建议值在 30 至 60μg·h/mL 之间。
本研究旨在探讨在肾移植后稳定>1 年的患者中，监测 MPA 预剂量浓度（C0）是否具有实际意义，并确定导致患者间 MPA C0 变异的因素。
本研究纳入了 86 名日本肾移植患者，他们在移植后接受了他克莫司治疗，并通过高效液相色谱法对 MPA C0 进行了>6 次分析，时间跨度超过 1 年。
在移植后 28 天和 1 年时，MPA AUC0-12 水平<30μg·h/mL 的受者 MPA C0 低于 2.0μg/mL，其灵敏度为 90.9%，特异性为 70.7%。在接受他克莫司治疗>1 年后，具有 UGT（1A1、1A9 和 2B7）或药物转运蛋白（SLCO1B3、ABCC2 和 ABCG2）基因型的受试者之间，其平均剂量调整后的 MPA C0 没有显著差异。然而，在多元回归分析中，接受他克莫司治疗>1 年后的平均剂量调整后的 MPA C0 与年龄（P=0.0035）、肌酐清除率（P=0.0001）和 1 年时的 MPA AUC0-12 （P=0.0147）显著相关。
为了保持 MPA AUC0-12>30μg·h/mL，使用高效液相色谱法确定，维持 MPA C0 所需的血浆阈值应设定为>2.0μg/mL。对于在移植后稳定>1 年的患者，使用监测他克莫司 C0 相同的样本继续监测 MPA C0，并在 1 年时额外评估 MPA AUC0-12，似乎是一种可行的选择。如果根据常规 MPA C0 信息似乎需要改变霉酚酸酯的剂量，建议使用有限采样策略来确定 MPA AUC0-12。
