Bunchman T, Navarro M, Broyer M, Sherbotie J, Chavers B, Tönshoff B, Birk P, Lerner G, Lirenman D, Greenbaum L, Walker R, Zimmerhackl L B, Blowey D, Clark G, Ettenger R, Arterburn S, Klamerus K, Fong A, Tang H, Thomas S, Ramos E
University of Alabama at Birmingham, 1600 7th Avenue South, Suite 735, Birmingham, Alabama 35233, USA.
Pediatr Nephrol. 2001 Dec;16(12):978-84. doi: 10.1007/s004670100006.
Mycophenolate mofetil (MMF) is widely used to prevent acute rejection in adults after renal, cardiac, and liver transplantation. This study investigated the safety, tolerability, and pharmacokinetics of MMF suspension in pediatric renal allograft recipients. One hundred renal allograft recipients were enrolled into three age groups (33 patients, 3 months to <6 years; 34 patients, 6 to <12 years; 33 patients, 12 to 18 years). Patients received MMF 600 mg/m2 b.i.d. concomitantly with cyclosporine and corticosteroids with or without antilymphocyte antibody induction. One year after transplantation, patient and graft survival (including death) were 98% and 93%, respectively. Twenty-five patients (25%) experienced a biopsy-proven (Banff grade borderline or higher) or presumptive acute rejection within the first 6 months post-transplantation. Analysis of pharmacokinetic parameters for mycophenolic acid (MPA) and mycophenolic acid glucuronide showed no clinically significant differences among the age groups. The dosing regimen of MMF 600 mg/m2 b.i.d. achieved the targeted early post-transplantation MPA 12-h area under concentration-time curve (AUC0-12) of 27.2 microg h per ml. Adverse events had similar frequencies among the age groups (with the exception of diarrhea, leukopenia, sepsis, and anemia, which were more frequent in the <6 years age group) and led to withdrawal of MMF in about 10% of patients. Administration of MMF 600 mg/m2 b.i.d. is effective in prevention of acute rejection, provides predictable pharmacokinetics, and is associated with an acceptable safety profile in pediatric renal transplant recipients.
霉酚酸酯（MMF）被广泛用于预防成人肾、心和肝移植后的急性排斥反应。本研究调查了MMF混悬液在小儿肾移植受者中的安全性、耐受性和药代动力学。100名肾移植受者被纳入三个年龄组（33例患者，3个月至<6岁；34例患者，6至<12岁；33例患者，12至18岁）。患者接受MMF 600 mg/m²，每日两次，同时服用环孢素和皮质类固醇，有或无抗淋巴细胞抗体诱导治疗。移植后一年，患者和移植物存活率（包括死亡）分别为98%和93%。25例患者（25%）在移植后前6个月内发生了经活检证实（Banff分级为临界或更高）或推定的急性排斥反应。霉酚酸（MPA）和霉酚酸葡糖苷酸的药代动力学参数分析显示，各年龄组之间无临床显著差异。MMF 600 mg/m²，每日两次的给药方案在移植后早期达到了目标MPA 12小时浓度-时间曲线下面积（AUC0-12）为每毫升27.2微克·小时。各年龄组不良事件的发生率相似（腹泻、白细胞减少、败血症和贫血除外，这些在<6岁年龄组中更常见），约10%的患者因不良事件停用MMF。MMF 600 mg/m²，每日两次给药可有效预防急性排斥反应，提供可预测的药代动力学，且在小儿肾移植受者中具有可接受的安全性。
