Weber L T, Shipkova M, Lamersdorf T, Niedmann P D, Wiesel M, Mandelbaum A, Zimmerhackl L B, Schütz E, Mehls O, Oellerich M, Armstrong V W, Tönshoff B
Division of Pediatric Nephrology, University Children's Hospital Heidelberg, Germany.
J Am Soc Nephrol. 1998 Aug;9(8):1511-20. doi: 10.1681/ASN.V981511.
Dosage guidelines for mycophenolate mofetil (MMF), an ester prodrug of the immunosuppressant mycophenolic acid (MPA), are still preliminary in children. This study compares the pharmacokinetics of MPA and its major metabolite MPA glucuronide (MPAG) in pediatric renal transplant recipients receiving 600 mg MMF/m2 body surface area twice a day to those of adults on the currently recommended oral dose of 1 g of MMF twice a day. Concentration-time profiles of 18 children (age, 10.7+/-0.72 yr; range, 5.9 to 15.3 yr) and 10 adults were investigated 1 and 3 wk after transplantation. Plasma concentrations of MPA and MPAG were measured by reverse-phase HPLC. Because MPA is extensively bound to serum albumin and only the free fraction is presumed to be pharmacologically active, the MPA free fraction was also analyzed by HPLC after separation through ultrafiltration. The areas under the concentration-time curves (AUC0-12) of total and free MPA throughout the 12-h dosing interval in children were, in general, comparable to the corresponding data in adult patients. The mean AUC0-12 of MPA and free MPA did not change significantly over the first 3 wk after transplantation, but there was substantial intra- and interindividual variation. MPAG-AUC0-12 values in children with primary renal transplant dysfunction were threefold higher than in those with functioning transplants. Renal impairment had no consistent effect on total MPA-AUC0-12 values, but the MPA free fraction in children (median, 1.65%; range, 0.40 to 13.8%) was significantly (r2=0.46) modulated by renal transplant function and serum albumin levels. In conclusion, concentration-time profiles of pediatric renal transplant recipients administered 600 mg MMF/m2 body surface area twice a day are comparable to those in adults on 1 g MMF twice a day in the first 3 wk after transplantation. Renal impairment and decreased serum albumin levels led to an increase in the free fraction of MPA and the free MPA-AUC0-12 values. Because the pharmacologic activity of MPA is a function of unbound drug concentration, these findings might be relevant for the pharmacodynamic effects of MPA.
霉酚酸酯（MMF）是免疫抑制剂霉酚酸（MPA）的酯前体药物，其在儿童中的用药指南仍处于初步阶段。本研究比较了接受每日两次600mg MMF/m²体表面积的儿科肾移植受者中MPA及其主要代谢产物MPA葡糖醛酸酯（MPAG）的药代动力学与接受当前推荐口服剂量每日两次1g MMF的成人的药代动力学。在移植后1周和3周对18名儿童（年龄，10.7±0.72岁；范围，5.9至1
