Comparison of two mycophenolate mofetil dosing regimens after hematopoietic cell transplantation.
Comparison of two mycophenolate mofetil dosing regimens after hematopoietic cell transplantation.
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DOI：
10.1038/bmt.2008.428
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发表时间：
2009-07
影响因子：
4.8
通讯作者：
Weisdorf, D.
中科院分区：
文献类型：
--
作者：
Jacobson, P.;El-Massah, S. F.;Rogosheske, J.;Kerr, A.;Long-Boyle, J.;DeFor, T.;Jennissen, C.;Brunstein, C.;Wagner, J.;Tomblyn, M.;Weisdorf, D.
关键词：
霉酚酸（MPA）是霉酚酸酯（MMF）的活性成分。低MPA暴露与较高的急性GVHD发生率和可能较差的植入相关。已经提出了造血细胞移植（HCT）中的治疗性血浆靶点，然而，在MMF剂量为2 g/天的成人患者中难以实现。在接受MMF 3 g/d和CYA的非清髓性HCT成人患者中前瞻性研究了霉酚酸酯的药代动力学。前15个个体每12 h接受1.5 g，后15个个体每8 h接受1 g。在每例静脉和口服给药患者中进行采样。两种给药方案的总MPA或游离MPA 24 h累积曲线下面积（AUC）、稳态浓度（Css）和谷浓度（波谷）均无差异（均P>0.01）。在3 g/天剂量下，仅分别有13-27%和20-53%的患者达到了之前提出的总MPA Css目标3 μg/ml和谷值≥1 μ g/ml。然而，在87-100%的受试者中，3 g/天方案很容易达到令人满意的0.600 μg*h/ml的未结合24小时累积AUC目标。当3 g/天的MMF分为两个或三个相等剂量时，每日MPA暴露量似乎无显著差异。
Mycophenolic acid (MPA)is the active component of mycophenolate mofetil (MMF). Low MPA exposure is associated with a higher incidence of acute GVHD and possibly worse engraftment. Therapeutic plasma targets have been proposed in hematopoietic cell transplantation (HCT), however, are difficult to achieve in adult patients with MMF doses of 2 g/day. Mycophenolate pharmaco-kinetics was prospectively studied in adults undergoing nonmyeloablative HCT who received MMF 3 g/day with CYA. The first 15 individuals received 1.5 g every 12 h and the second 15 received 1 g every 8 h. Sampling was performed in each patient with i.v. and oral administration. There were no differences in total or unbound MPA 24-h cumulative area under the curves (AUCs), concentrations at steady state (Css)or troughs between the two dosing regimens (all P>0.01). The previously proposed total MPA Css target of 3 μg/ml and trough ≥1 μ/ml were achieved in only 13–27% and 20–53% of patients, respectively, on 3 g/day. However, the 3 g/day regimens readily achieved satisfactory unbound 24-h cumulative AUC targets of 0.600 μg*h/ml in 87–100% of subjects. There appears to be no significant difference in daily MPA exposure when MMF of 3 g/day is divided into two or three equal doses.
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