Jacobson Pamala, Huang Jaiyin, Rydholm Nancy, Tran Myhang, Defor Todd, Tolar Jakub, Orchard Paul J
Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.
J Clin Pharmacol. 2008 Apr;48(4):485-94. doi: 10.1177/0091270007313326. Epub 2008 Feb 22.
Little is known about dosing of mycophenolate mofetil in pediatric hematopoietic cell transplant recipients; therefore, dosing strategies using other settings have been extended to this population. The authors studied pharmacokinetics in 19 children (median 17 months) undergoing myeloablative hematopoietic cell transplant and receiving prophylactic mycophenolate and cyclosporine. All subjects except 2 received mycophenolate 15 mg/kg intravenously every 8 hours. The median (range) total mycophenolic acid area under the concentration-time curve (AUC)(0-8) was 12.6 mcg.h/mL (4.9-49.2), and unbound mycophenolic acid AUC(0-8) was 0.274 mcg.h/mL (0.037-1.4). Total and unbound mycophenolic acid trough concentrations were 0.27 (0.03-2.9) and 0.005 (0-0.034) mcg/mL, respectively. Mycophenolic acid trough concentrations were not good surrogates for overall exposure (AUC(0-8)), r(2) < or = 0.55. Mycophenolate dose requirements are higher in pediatric hematopoietic cell transplant recipients relative to pediatric organ transplant recipients. Children undergoing hematopoietic cell transplant should receive a mycophenolate mofetil dose of at least 15 mg/kg intravenously every 8 hours when used in combination with cyclosporine to achieve systemic concentrations near those proposed to be therapeutic in the adult hematopoietic cell transplant population.
关于儿科造血细胞移植受者中霉酚酸酯的给药情况，人们所知甚少；因此，其他情况下的给药策略已扩展至该人群。作者对19名（中位年龄17个月）接受清髓性造血细胞移植并接受预防性霉酚酸酯和环孢素治疗的儿童进行了药代动力学研究。除2名受试者外，所有受试者均每8小时静脉注射15mg/kg霉酚酸酯。浓度-时间曲线下霉酚酸的中位（范围）总面积（AUC）(0 - 8)为12.6mcg·h/mL（4.9 - 49.2），游离霉酚酸AUC(0 - 8)为0.274mcg·h/mL（0.037 - 1.4）。霉酚酸的总谷浓度和游离谷浓度分别为0.27（0.03 - 2.9）和0.005（0 - 0.034）mcg/mL。霉酚酸谷浓度并非总体暴露（AUC(0 - 8)）的良好替代指标，r(2)≤0.55。相对于儿科器官移植受者，儿科造血细胞移植受者的霉酚酸酯剂量需求更高。接受造血细胞移植的儿童在与环孢素联合使用时，应每8小时静脉注射至少15mg/kg霉酚酸酯，以达到接近成人造血细胞移植人群中建议的治疗浓度的全身浓度。
