Pharmacokinetics of intravenous mycophenolate mofetil in allogeneic hematopoietic stem cell-transplanted Japanese patients
Pharmacokinetics of intravenous mycophenolate mofetil in allogeneic hematopoietic stem cell-transplanted Japanese patients
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静脉注射吗替麦考酚酯在异基因造血干细胞移植日本患者中的药代动力学
DOI：
10.1007/s00280-018-3550-7
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发表时间：
2018
影响因子：
3
通讯作者：
Minami Hironobu
中科院分区：
文献类型：
--
作者：
Kurata Keiji;Yakushijin Kimikazu;Okamura Atsuo;Yamamori Motohiro;Ichikawa Hiroya;Sakai Rina;Mizutani Yu;Kakiuchi Seiji;Miyata Yoshiharu;Kitao Akihito;Kawamoto Shinichiro;Matsuoka Hiroshi;Murayama Tohru;Minami Hironobu
霉酚酸酯（Mycophenolate mofetil，MMF）在日本异基因造血干细胞移植（allo-SCT）患者中的应用日益增多。由于在亚洲人口的霉酚酸酯的药代动力学数据是有限的，我们进行了这项investigation.MethodsIntravenous霉酚酸酯（1000毫克/剂），给药沿着环孢素或他克莫司10天后，异基因造血干细胞移植，它是每8小时在外周血干细胞和骨髓移植患者，每12小时在脐带血移植患者。从第11天开始，以相同剂量经口给予MMF。结果在第2、9和16天，霉酚酸（MPA）的AUC 0 − τ分别为31.9 ± 3.4、26.2 ± 2.4和21.0 ± 2.2 μ g * h/mL，平均Ctrough分别为0.25、0.35和0.37 μ g/mL，Cmax分别为10.8、9.2和5.5 μ g/mL，分别静脉给予MMF后的AUC 0 − tau和Cmax显著高于口服MMF后。所有患者均在18天的中位时间内表现出成功的中性粒细胞植入。在2名患者中观察到皮肤的II级急性移植物抗宿主病（GvHD），1名患者发展为有限的慢性GvHD。观察到一过性和可治愈的III级口腔粘膜炎和腹泻的个体病例;但是，未停用MMF。没有其他严重的并发症或感染observed.ConclusionsIntraperitoneadministered霉酚酸酯是安全的，并可能有效地实现更高的MPA血浆浓度的GvHD预防后，异基因造血干细胞移植在日本患者。
PurposeMycophenolate mofetil (MMF) is increasingly used among Japanese patients undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT). Because pharmacokinetic data for MMF in the Asian population are limited, we conducted this investigation.MethodsIntravenous MMF (1000 mg/dose) was administered to 10 patients along with cyclosporine or tacrolimus for 10 days after allo-SCT; it was administered every 8 h in peripheral blood stem cell- and bone marrow-transplanted patients, and every 12 h in cord blood-transplanted patients. MMF was administered orally at the same dose from day 11. Plasma concentrations of mycophenolic acid (MPA) were measured by high-performance liquid chromatography.ResultsThe MPA AUC0 − tauwas 31.9 ± 3.4, 26.2 ± 2.4, and 21.0 ± 2.2 µg*h/mL, the meanCtroughwas 0.25, 0.35, and 0.37 µg/mL, and theCmaxwas 10.8, 9.2, and 5.5 µg/mL on days 2, 9, and 16, respectively. The AUC0 − tauandCmaxwere significantly higher after intravenous MMF dosing than after oral MMF dosing. All patients exhibited successful neutrophil engraftments in a median time of 18 days. Grade II acute graft-versus-host disease (GvHD) of the skin was observed in two patients, and one patient developed limited chronic GvHD. Individual cases of transient and curable grade III oral mucositis and diarrhea were observed; however, MMF was not discontinued. No other severe complications or infections were observed.ConclusionsIntravenously administered MMF was safe and possibly effective in achieving higher MPA plasma concentrations for GvHD prophylaxis after allo-SCT in Japanese patients.