Yau Wai-Ping, Vathsala Anantharaman, Lou Huei-Xin, Chan Eli
Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543, Republic of Singapore.
Nephrol Dial Transplant. 2007 Dec;22(12):3638-45. doi: 10.1093/ndt/gfm468. Epub 2007 Jul 19.
A standard fixed dose of 2 g/day of mycophenolate mofetil (MMF), irrespective of total body weight (TBW), is recommended when used in combination with cyclosporine and corticosteroids in renal transplantation.
To determine the optimal MMF dose in a population with wide variation in TBW, steady-state pharmacokinetics of mycophenolic acid (MPA) was performed in 53 Asian (Chinese, Malay, Indian, Eurasian) renal transplant recipients (RTX) receiving MMF [250-1000 mg twice daily (BD)] for at least 3 months. Blood samples were collected at 0, 0.5, 1, 1.5, 2 and 6 h after the MMF dose and total MPA quantified using HPLC.
Drug exposure, as evaluated by AUC(ss, 0-12), demonstrated a significant positive correlation with TBW-adjusted MMF dose (outliers omitted: r(2) = 0.49, P < 0.0005). An AUC(ss, 0-12) of 45 mg h/l could be attained with an MMF dose of 12 mg/kg BD.
This study proposes that MMF should be dosed based on TBW rather than a fixed dose regimen in RTX.
在肾移植中，当霉酚酸酯（MMF）与环孢素和皮质类固醇联合使用时，推荐使用标准固定剂量2克/天，而不考虑总体重（TBW）。
为了确定在TBW差异较大的人群中MMF的最佳剂量，对53名接受MMF[250 - 1000毫克，每日两次（BD）]至少3个月的亚洲（中国、马来、印度、欧亚混血）肾移植受者（RTX）进行了霉酚酸（MPA）的稳态药代动力学研究。在MMF给药后0、0.5、1、1.5、2和6小时采集血样，并使用高效液相色谱法对总MPA进行定量。
通过AUC(ss, 0 - 12)评估的药物暴露与TBW调整后的MMF剂量呈显著正相关（剔除异常值：r(2) = 0.49，P < 0.0005）。MMF剂量为12毫克/千克BD时，AUC(ss, 0 - 12)可达到45毫克·小时/升。
本研究提出，在肾移植受者中，MMF应根据TBW给药，而不是采用固定剂量方案。
