Department of Hospital Pharmacy, Erasmus Medical Center, Rotterdam, The Netherlands.
Transplantation. 2010 Mar 15;89(5):595-9. doi: 10.1097/TP.0b013e3181ca7d84.
To better define subpopulations in which achieving adequate mycophenolic acid (MPA) concentrations quickly would be important, a post hoc exploratory analysis on the fixed-dose concentration-controlled database was performed, comparing high- versus low-risk renal transplant patients.
Renal transplant patients were treated with mycophenolate mofetil, corticosteroids, and cyclosporine A or tacrolimus. Patients were defined as "high risk" if they had one or more of the following characteristics: delayed graft function, second or third transplantation, panel reactive antibodies >15%, four or more human leukocyte antigen mismatches, or were of black race.
A total of 549 patients (61%) were classified as high risk, of whom 284 were on cyclosporine A treatment and 265 on tacrolimus. In high-risk patients, the difference in rejection incidence was 14.3% in the MPA-area under the concentration (AUC) less than 30 mg hr/L vs. 7.8% in the MPA-AUC more than or equal to 30 mg hr/L groups (P=0.025) during the first month after transplantation; whereas, in low-risk patients, there were similar rejection rates (5.7% vs. 4.5%). In the subgroup of high-risk tacrolimus-treated patients, the difference in acute rejection incidence in the first month between patients with MPA-AUC0-12 less than or more than or equal to 30 mg hr/L was most pronounced: 16 of 67 patients (23.9%) vs. 18 of 173 patients (10.4%); P=0.012.
The incidence of acute rejection is higher in high-risk patients if MPA-AUC0-12 is below 30 mg hr/L. In contrast, a difference in acute rejection incidence in low-risk patients with MPA-AUC0-12 less than or more than or equal to 30 mg hr/L was not observed. This supports the use of a higher mycophenolate mofetil starting dose in selected patient populations early after transplantation.
为了更好地确定哪些亚组人群需要尽快达到足够的霉酚酸（MPA）浓度，我们对固定剂量浓度控制数据库进行了一项事后探索性分析，比较了高危和低危肾移植患者。
肾移植患者接受霉酚酸酯、皮质类固醇、环孢素 A 或他克莫司治疗。如果患者具有以下一种或多种特征，则定义为“高危”：移植物功能延迟、二次或三次移植、群体反应性抗体 >15%、四个或更多人类白细胞抗原错配、或为黑人。
共有 549 名患者（61%）被归类为高危，其中 284 名患者接受环孢素 A 治疗，265 名患者接受他克莫司治疗。在高危患者中，移植后第一个月 MPA 浓度下面积（AUC）<30 mg·hr/L 组的排斥发生率为 14.3%，而 MPA-AUC≥30 mg·hr/L 组为 7.8%（P=0.025）；而在低危患者中，排斥率相似（5.7% vs. 4.5%）。在高危他克莫司治疗患者亚组中，MPA-AUC0-12<30 和≥30 mg·hr/L 两组患者在第一个月发生急性排斥反应的发生率差异最大：67 名患者中有 16 名（23.9%），173 名患者中有 18 名（10.4%）；P=0.012。
如果高危患者 MPA-AUC0-12 低于 30 mg·hr/L，则急性排斥反应的发生率更高。相比之下，在 MPA-AUC0-12<30 和≥30 mg·hr/L 的低危患者中，急性排斥反应发生率没有差异。这支持在移植后早期选择特定患者人群使用更高的霉酚酸酯起始剂量。
