Mycophenolate mofetil (Cellcept)

Mycophenolate mofetil (MMF) is a new immunosuppressive drug designed to inhibit inosine monophosphate dehydrogenase (IMPDH). IMPDH is a key enzyme in the purine synthesis pathway of lymphocytes. IMPDH is crucially important for the proliferative responses of human T- and B-lymphocytes. Therefore, inhibition of IMPDH leads to selective lymphocyte suppression. Following successful testing in different in vitro and animal models, MMF entered clinical trials, where it has been used in combination with cyclosporin and steroids. MMF has rapid and complete absorption following oral administration. Pilot studies suggested a significant reduction in the incidence of rejection at doses of 1 - 3 g/day. These data led to the initiation of 3 pivotal trials, in which MMF was compared against different standard immunosuppressive protocols. Nearly 1500 patients were enrolled in these 3 randomised, double-blind, multicentre studies of the addition of MMF to standard immunosuppressive protocols for the prevention of acute renal allograft rejection. After six months, the rate of biopsy-proven rejection was significantly reduced. The adverse event profile resembles that of triple therapy with azathioprine: primarily involving the gastrointestinal (GI) tract, the haematopoietic system and the occurrence of opportunistic infections. MMF affords improved immunosuppressive therapy following renal, and probably other solid organ, transplantation. It is licensed for the prevention of acute renal allograft rejection in most countries around the world.     

实体器官移植患者霉酚酸的药动学特征及其影响因素

目的：霉酚酸（mycophenolic acid,MPA）已广泛用于预防实体器官移植术后的排斥反应和自身免疫性疾病的治疗。但MPA的药动学特征具有明显的个体差异。本文综述了相关文献报导,旨在为临床开展广泛和深入的研究提供有益的参考。方法：综述霉酚酸在实体器官移植临床药动学研究及影响因素的文献报道。影响因素包括了不同器官移植、年龄、性别、种族、血清白蛋白（ALB）、合用药物、并发症以及基因多态性的影响。结果：国内外研究结果在不同器官移植、合用药物、种族、肾功能损伤等方面具有相似的报道,而在其他影响因素方面存在研究范围及研究结果的差异。结论：MPA药动学参数影响因素众多且不易控制,因此应继续进行多方面、大样本的临床考察,控制药动学的影响因素,得出确定并能达成共识的临床监测指标,从而更好的取得临床疗效。     

肾移植患者吗替麦考酚酯药时曲线下面积与不良反应的相关性

目的:探讨肾移植患者吗替麦考酚酯(MMF)血药浓度与药品不良反应(ADR)发生的相关性。方法:通过均相酶免疫法(EMIT)测定血浆麦考酚酸药时曲线下面积(MPA-AUC),对某院2012年2月-2014年2月599例肾移植患者发生药品不良反应进行回顾性分析。结果:肾移植患者住院情况在不同性别、年龄、移植时间存在显著性差异(P<0.05),移植时间超过1个月患者各类ADR发生与MPA-AUC呈线性相关(P=0.0162),且带状疱疹的发生率在MPA-AUC值<30 mg·L^-1·h^-1、30~60 mg·L^-1·h^-1、>60 mg·L^-1·h^-1中,有显著性差异(P=0.014)。结论:肾移植术后各类ADR的发生与MPA-AUC相关,对其监测具有一定意义。采取浓度控制MMF给药剂量更加有利于药物的合理使用。     

Mycophenolate mofetil in solid-organ transplantation

This review focuses on the use of mycophenolate mofetil (MMF) as an immunosuppressive agent in solid-organ transplantation. MMF, a non-competitive inhibitor of inosine monophosphate dehydrogenase, blocks de novo purine synthesis in T and B lymphocytes, resulting in the selective inhibition of proliferation of these cells in response to antigenic stimuli. MMF may also promote apoptosis of these cells. The immunosuppressive ability of MMF is thought to derive mainly from the inhibition of inosine monophosphate dehydrogenase. The other effects of MMF include suppression of antibody synthesis by B lymphocytes, inhibition of proliferation of smooth muscle cells in culture and impaired glycosylation of adhesion molecules. MMF may exhibit anti-inflammatory effects resulting from decreased activity of the inducible form of nitric oxide synthase, a consequence of depletion of tetrahydrobiopterin, which leads to decreased generation of peroxynitrite, a pro-inflammatory molecule. The pharmacokinetics, pharmacodynamics and principles underlying therapeutic drug monitoring of MMF are reviewed. The results of the pivotal clinical trials of MMF in kidney and heart transplantation are discussed and a summary of the major studies demonstrating a positive effect of MMF on renal transplantation outcomes is presented. The use of MMF in the context of ABO-incompatible renal transplantation, renal transplantation in highly sensitised and cross-match positive recipients, humoral rejection of renal allografts, chronic allograft nephropathy and steroid/calcineurin inhibitor minimisation in renal transplantation are also discussed.     

吗替麦考酚酯胶囊在健康人体中的相对生物利用度

目的：评价吗替麦考酚酯胶囊在健康人体的相对生物利用度。方法：采用高效液相色谱-紫外检测法测定。18名健康志愿者采用两制剂双周期交叉试验方法，分别测定口服两种制剂后不同间隔时间的血药浓度，并依次计算药动学参数评价胶囊的生物利用度。结果：受试者口服1g吗替麦考酚酯胶囊参比制剂和受试制剂的Gmax分别为（41．5±11．8）mg·L^-1和（37．2±10．0）mg·L^-1；tmax为（0．53±0．19）h和（0．54±0．18）h；t（1/2）为（13．6±7．6）h和（11．6±6．2）h；AUC（0-24）分别为（62．4±12．0）mg·h·L^-1和（63．7±15．1）mg·h·L^-1。受试制剂的相对生物利用度为（102±12）%。结论：两种制剂的主要药动学参数，经对数转换后进行交叉试验的方差分析与双单侧t检验表明．两种制剂的AUC及有关的药动学参数具有生物等效性。     

吗替麦考酚酯在自身免疫性疾病患者体内的药代动力学研究

目的探讨免疫抑制剂吗替麦考酚酯(MMF)在自身免疫性疾病患者体内首次给药和稳态后的药代动力学。方法自身免疫性疾病患者14例,口服吗替麦考酚酯0.75 g,q12 h,连续服药7 d达稳态,用高效液相色谱法测定MMF的活性代谢物麦考酚酸(MPA)及二级代谢物酚化葡萄糖醛麦考酚酸(MPAG)的血药浓度,并评价2种代谢物的体内暴露药量与患者肾功能的关系。结果 MPA首次服药及稳态后的Cmax分别为(8.45±7.54),(10.89±4.37)mg·L-1,AUC0-12h分别为(41.07±49.26),(55.09±41.74)mg·h·L-1;MPAG首次及稳态后的Cmax分别为(41.24±28.57),(67.63±36.98)mg·L-1,AUC0-12h分别为(487.25±326.53),(720.79±413.86)mg·h·L-1;两者在患者个体间药代动力学参数差异均较大,且稳态后的AUC0-12h与首次给药相比均明显增大(P<0.05);MPAG的体内暴露药量与肾功能存在明显负相关(P<0.05),而MPA的体内暴露药量与患者肾功能无明显相关性(P>0.05)。结论自身免疫性疾病患者同方案给药后,MPA及MPAG血药浓度及药代动力学个体间差异大,且在体内存在明显蓄积现象。     

3×3拉丁方设计评价国产麦考酚吗乙酯片、胶囊与其进口制剂的生物等效性

目的3×3拉丁方研究国产麦考酚吗乙酯片剂、胶囊剂与进口麦考酚吗乙酯胶囊(商品名:骁悉)的生物等效性。方法24名健康男性志愿者随机交叉单剂量口服国产麦考酚吗乙酯片剂、胶囊剂和进口麦考酚吗乙酯胶囊500 mg,以HPLC法测定血药浓度,计算各药动学参数和相对生物利用度,并以WinNonlin程序计算药动学参数,评价生物等效性。结果国产麦考酚吗乙酯片剂、胶囊和进口麦考酚吗乙酯胶囊药-时曲线符合线性动力学一室开放模型,AUC0→48分别是(39.74±8.61)、(38.06±9.01)和(36.21±9.17)mg.h.L-1;AUC0→∞:(44.02±10.62)(、40.91±9.54)和(39.82±9.21)mg.h.L-1;ρmax:(20.19±9.63)、(17.42±6.03)和(18.48±7.06)mg.L-1;tmax:(0.74±0.64)(、0.72±0.35)和(0.56±0.20)h;t12:(13.43±4.58)、(12.20±3.08)和(13.59±5.40)h;MRT:(14.95±5.85)(、13.42±2.83)和(14.40±5.47)h。结论国产麦考酚吗乙酯片剂、胶囊与进口麦考酚吗乙酯胶囊具有生物等效性。     

3×3拉丁方设计评价国产麦考酚吗乙酯片、胶囊与其进口制剂的生物等效性

目的 3×3拉丁方研究国产麦考酚吗乙酯片剂、胶囊剂与进口麦考酚吗乙酯胶囊（商品名：骁悉）的生物等效性.方法 24名健康男性志愿者随机交叉单剂量口服国产麦考酚吗乙酯片剂、胶囊剂和进口麦考酚吗乙酯胶囊500 mg，以HPLC法测定血药浓度，计算各药动学参数和相对生物利用度，并以WinNonlin程序计算药动学参数，评价生物等效性.结果 国产麦考酚吗乙酯片剂、胶囊和进口麦考酚吗乙酯胶囊药-时曲线符合线性动力学-室开放模型，AUC0→48分别是（39.74±8.61）、（38.06±9.01）和（36.21±9.17）mg·h·L^-1 AUC0→∞：（44.02±10.62）、（40.91±9.54）和（39.82±9.21）mg·h·L^-1 ρmax：（20.19±9.63）、（17.42±6.03）和（18.48±7.06）mg·L^-1 tmax：（0.74±0.64）、（0.72±0.35）和（0.56±0.20）h t1/2：（13.43±4.58）、（12.20±3.08）和（13.59±5.40）h MRT：（14.95±5.85）、（13.42±2.83）和（14.40±5.47）h.结论 国产麦考酚吗乙酯片剂、胶囊与进口麦考酚吗乙酯胶囊具有生物等效性.     

麦考酚酸酯在肾移植中的应用

目的：观察麦考酚酸酯（ ｍｙｍcoｐｈｅｎｏｌａｔｅｍｏｆｅｔｉｌ,ＭＭＦ）预防移植肾急性排斥的安全性及有效性。方法：４０例肾移植病人分为２组,２０例［男性１２例,女性 ８例,年龄（４３ ± ｓ １０） ａ］为治疗组,给予ＭＭＦ1ｇ, ｐｏ, ｂｉｄ;另 ２０例［男性 １３例,女性 ７例,年龄（４５±１１） ａ］为对照组,给予硫唑嘌呤（Ａｚａ） １５０ｍｐ,ｐｏ, ｑｎ。共 ６ ｍｏ。结果： ＭＭＦ组急性排斥反应发生率为０,Ａｚａ组为２例,２组间差异无显著意义（Ｐ＞０．０５）。２组病人的消化道反应、肝中毒、感染等并发症的发生率的差异无显著意义（Ｐ＞０．０５）。结论：ＭＭＦ是一种能预防移植肾急性排斥反应的安全、有效的免疫抑制剂。     

麦考酚酸酯分散片在健康志愿者体内的生物等效性评价

目的:评价麦考酚酸酯(MMF)分散片与其胶囊(商品名:骁悉)的生物等效性。方法:20名健康志愿者按随机双周期交叉试验方案设计,单剂量口服MMF分散片或其胶囊各500mg,采用RP-HPLC荧光检测法测定MMF的活性代谢产物麦考酚酸(MPA)的血药浓度。用非房室模型计算MPA药动学参数,用方差分析和双单侧t检验评价两者之间的生物等效性。结果:MMF分散片与其胶囊的主要药动学参数AUC0-48分别为(32.7±6.6)与(30.6±9.9)mg.L-1.h,AUC0-∞分别为(35.8±7.4)与(33.3±10.2)mg.L-1.h,Cmax分别为(17.0±4.5)与(15.8±4.8)mg.L-1,tmax分别为(0.45±0.29)与(0.6±0.3)h,t1/2β分别为(13.4±4.7)与(12.7±4.4)h。MMF分散片相对于其胶囊的生物利用度F为(111.6±24.0)%,经统计学检验,两者差异无显著性(P>0.05)。结论:MMF分散片与其胶囊具有生物等效性。     

吗替麦考酚酯分散片在健康人体的药代动力学和生物等效性

目的研究国产吗替麦考酚酯(MMF)分散片(免疫抑制剂)和其进口胶囊在健康人体的生物等效性。方法用随机自身对照双周期交叉试验设计,18名男性健康志愿者口服MMF分散片或胶囊各1.0g,用高效液相色谱法测定MMF的活性代谢产物麦考酚酸(MPA)的血药浓度,用非房室模型计算MPA的药代动力学参数。结果MMF分散片与胶囊的药代动力学参数如下:tmax分别为(0.68±0.21),(0.81±0.18)h;Cmax分别为(25.58±4.79),(26.47±3.67)mg·L-1;AUC(0-48)分别为(59.19±9.23),(58.32±9.28)mg.h.L-1;t1/2分别为(15.12±3.17),(16.14±4.22)h。国产吗替麦考酚酯分散片中麦考酚酸相对于胶囊的相对生物利用度为(101.5±10.3)%。结论2制剂在人体内生物等效。     

吗替麦考酚酯分散片的相对生物利用度及生物等效性

目的:研究吗替麦考酚酯分散片和吗替麦考酚酯胶囊在健康志愿者中的药动学及生物等效性。方法:根据交叉试验方案口服单剂量(1 000mg)两种吗替麦考酚酯制剂,采用高效液相色谱法测定血浆中霉酚酸的浓度。结果:吗替麦考酚酯分散片和吗替麦考酚酯胶囊(对照药)的tmax分别为(0.51±0.29)h和(0.54±0.26)h;Cmax分别为(53.6±22.2)mg.L-1和(52.4±18.3)mg.L-1;AUC0→48分别为(133.7±43.6)mg.h.L-1和(142.8±46.2)mg.h.L-1;分散片相对于胶囊的生物利用度为(96.1±19.7)%。经配对检验,结果表明,两种制剂的主要药动学参数Cmax、AUC0→48的差异无显著性(P>0.05)。结论:吗替麦考酚酯分散片和吗替麦考酚酯胶囊为生物等效制剂。     

兔血浆中霉酚酸酯的活性代谢物霉酚酸的HPLC测定及其药代动力学研究

目的建立霉酚酸兔血药浓度测定方法 ,并进行了灌胃后药代动力学研究。方法采用HPLC 二极管阵列检测器测定血药浓度。血样采用乙醚萃取 ;色谱柱 :HypersilODS2 (2 0 0mm×4 6mm ,5 μm) ;流动相 :0 0 5mol·L-1KH2 PO4 CH3 CN(5 5∶45 ,pH 2 5 ) ;检测波长 :2 1 5nm ;流速 :1 0mL·min-1。结果霉酚酸血药浓度线性范围为 0 1 6～ 1 9 98μmol·L-1(r =0 9996,n =8) ,血浆最低检测浓度为 0 0 3 μmol·L-1,高、中、低 3种浓度平均回收率分别为 :(1 0 3 2 5± 6 3 2 ) %、(99 63± 2 75 ) %、(1 0 2 47± 3 1 8) % ,兔灌胃后主要的药代动力学参数分别为 :达峰浓度cmax为(8 2 7± 6 1 2 ) μmol·L-1,达峰时间tmax为 (0 49± 0 1 7)h ,消除半衰期t1/ 2 为 (3 1 2± 0 94)h ,药时曲线下面积AUC0 -t为 (1 3 0 8± 9 0 8) μmol·h·L-1,AUC0 -∞ 为 (1 3 80± 8 93 )mg·h·L-1。结论为霉酚酸的血药浓度监测及药动学研究提供了实验方法。     

霉酚酸酯替代硫唑嘌呤在肾移植中的应用

目的 观察霉酚酸酯(MMF)替代硫唑嘌呤(Aza)在预防肾移植术后急性排斥中的作用。方法 回顾性分析我院95例肾移植后应用皮质激素(Perd),环孢素(CsA),MMF(或)硫唑嘌呤(Aza)三联免疫抑制剂治疗,其中分成MMF组57例,Aza组38例,MMF组适当减少环孢素用量。结果 MMF组发生急性排斥率为8．89%(5／57),Aza组为23．7%(9／38)。结论 以MMF代替Aza应用于肾移植术后,可以减少术后急性排斥及CsA的用量,减少药物的肝肾毒性。     

Pre-dose plasma concentration monitoring of mycophenolate mofetil in patients with autoimmune diseases

Aim

To date, neither the benefit of mycophenolic acid (MPA) therapeutic drug monitoring (TDM), the prodrug of mycophenolate mofetil (MMF), nor the optimal monitoring technique have been established in autoimmune diseases. This study was undertaken to confirm, in a cohort of new patients, the plasma MPA thresholds previously published in patients with systemic lupus erythematosus (SLE) or vasculitis.

Methods

MPA areas under the concentration–time curves between 0 and 12 h, 12 h trough concentrations and pre-dose concentrations (C₀) were determined for 23 patients with SLE and 21 with systemic vasculitis. The relationship between patients'' pharmacokinetic (PK) variables and their clinical outcomes during follow-up were analyzed.

Results

In both autoimmune diseases, at PK assessment, median MPA C₀ for patients with uncontrolled disease was significantly lower than that of patients with stable disease or in remission, 1.6 mg l^–1 (IQR 0.9–2.1 mg l^–1) vs. 2.95 mg l^–1 (IQR 1.38–3.73 mg l^–1) for SLE (P = 0.048) and 1.55 mg l^–1 (IQR 0.98–2.18 mg l^–1) vs. 3 mg l^–1 (IQR 2.2–4.4 mg l^–1) for vasculitis (P = 0.016). According to our receiver operating characteristics curve analysis, a C₀ threshold of 2.5–3 mg l^–1 was best able to discriminate a flare (SLE: 88% sensitivity, 80% specificity; vasculitis: 100% sensitivity, 90% specificity). Patients with C₀ ≥ 2.5–3 mg l^–1 at inclusion had better clinical outcomes during the 12 months following PK assessment.

Conclusion

Provided that the benefit of TDM in patients with autoimmune diseases could be confirmed by randomized, controlled trials, it might be based on the C₀ measured approximately 12 h post-dose.     

霉酚酸酯在肾移植术后的临床应用

目的:建立霉酚酸酯(MMF)与环孢素A(CsA)及皮质激素(Pred)合用时CsA的治疗窗,分析霉酚酸酯在肾移植术后的临床疗效.方法:对临床164份病例资料进行回顾性分析.结呆:MMF方案CsA的治疗窗为:1mo内为150～300ng/ml,1～3mo 120～260ng/ml,3～6mo 110～225ng/ml;MMF方案中毒反应、排异反应发生均低于经典三联方案(CsA 硫唑嘌呤Aza Pred).结论:MMF方案优于经典三联方案,可安全、有效地预防肾移植术后急慢性排斥及中毒反应的发生率.     

Stability and pharmacokinetic studies of a new immunosuppressant,mycophenolate mofetil (RS-61443), in rats

Mycophenolate mofetil (MPM), a new immunosuppressant, is a morpholinoethyl ester of mycophenolic acid (MPA). The enzymatic and non-enzymatic hydrolysis was studied in an artifical digestive fluid, rat plasma, and tissue homogenates. MPM was chemically stable in the artificial digestive fluid. In rat tissue homogenates and plasma, MPM was rapidly hydrolysed to MPA. The conversion rate of MPM to MPA in various rat tissue homogenates was in the order of liver > kidney > plasma > small-intestinal epithelial cells. After the intravenous injection of MPM at 16.7 mg kg^?1, the terminal elimination half-life,-t_1/2β, was 4.74 ± 0.33 (mean ± SD)h, and the area under the plasma concentration versus time curve, AUC, was 48.78 ± 6.01 μg h mL^?1. After intraduodenal (ID) administration of MPM at 16.7 mg kg^?1, t_1/2β was 3.92 ± 1.05 h, and the AUC was 38.08 ± 8.30 μg h mL^?1. The systemic availability of MPA after ID MPM dosing was 1.52 times higher than that after ID administration of MPA. This result supports the usefulness of MPM as an oral produrg of MPA as a new oral immunosuppressant.     

吗替麦考酚酯胶囊和麦考酚钠肠溶片在早期肾移植患者中的药动学

目的：探讨肾移植术后早期患者口服吗替麦考酚酯胶囊（MMF）和麦考酚钠肠溶片（EC-MPS）的药动学特点,为临床合理用药提供依据。方法：选取26例肾移植患者,按随机数字表法分为MMF组（n=13）和EC-MPS组（n=13）,两组患者分别于术后第1天给予MMF（750 mg q12 h）或EC-MPS（720 mg q12 h）、他克莫司、甲泼尼龙预防排斥反应。于术后第7天的早上服药前及服药后0.5,1,1.5,2,3,4,6,8,10,12 h采集静脉血样3 mL,采用UPLC-UV分析方法测定霉酚酸（MPA）血浆浓度。以 DAS 2.0药动学软件进行药动学分析,所有与剂量相关的两组药动学参数分别进行了剂量校正（C_max/D,C₀/D,AUC_{0-12 h}/D及AUMC_{0-12 h}/D）。用SPSS 17.0软件进行统计学分析。结果：术后第7天MMF和EC-MPS的主要药动学参数t_max分别为（1.54±0.9）h和（2.19±1.56）h（P> 0.05）;C_max/D分别为（5.12±2.83）mg·L^-1·g^-1和（9.51±7.38）mg·L^-1·g^-1（P> 0.05）;AUC_{0-12 h}/D分别为（19.13±7.78）mg·h·L^-1·g^-1和（25.96±11.78）mg·h·L^-1·g^-1（P> 0.05）。两组患者的药-时曲线个体间差异均较大,大部分患者观察到有双峰现象,极个别患者观察到有多峰。MMF组和EC-MPS组患者的MPA-AUC_{0-12 h}低暴露组比例分别为84.6%和46.15%,目标暴露组比例分别为15.4%和46.15%,仅有1例EC-MPS组患者为高暴露组。结论：MMF和EC-MPS在早期肾移植患者体内的药动学个体差异较大,需要常规监测MPA-AUC_{0-12 h},同时可结合C₀作为参考,以指导临床调整用药剂量。MMF和EC-MPS常规剂量下的MPA-AUC_{0-12 h}在早期肾移植患者中偏低,建议增加给药剂量。     

Population pharmacokinetics of mycophenolic acid in children and young people undergoing blood or marrow and solid organ transplantation

AIMS

To characterize the population pharmacokinetics of mycophenolic acid (MPA) and evaluate dose regimens using a simulation approach and accepted therapeutic drug monitoring targets in children and young people undergoing blood or marrow, kidney and liver transplantation.

METHODS

MPA concentration–time data were collected using an age specific sampling protocol over 12 h. Some patients provided randomly timed but accurately recorded blood samples. Total and unbound MPA were measured by HPLC. NONMEM was employed to analyze MPA pharmacokinetic data. Simulations (n = 1000) were conducted to assess the suitability of the MPA dose regimens to maintain total MPA AUC(0,12 h) within the range 30 and 60 mg l⁻¹ h associated with optimal outcome.

RESULTS

A two-compartment pharmacokinetic model with first-order elimination best described MPA concentration–time data. Population mean estimates of MPA clearance, inter-compartmental clearance, volumes of distribution in the central and peripheral compartments, absorption rate constant and bioavailability were 6.42 l h⁻¹, 3.74 l h⁻¹, 7.24 l, 16.8 l, 0.39 h⁻¹ and 0.48, respectively. Inclusion of bodyweight and concomitant ciclosporin reduced the inter-individual variability in CL from 54.3% to 31.6%. Children with a bodyweight of 10 kg receiving standard MPA dose regimens achieve an MPA AUC below the target range suggesting they may be at a greater risk of acute rejection.

CONCLUSIONS

The population pharmacokinetic model for MPA can be used to explore dosing guidelines for safe and effective immunotherapy in children and young people undergoing transplantation.     

霉酚酸在肝移植病人体内的药代动力学研究

目的研究免疫抑制剂霉酚酸酯(MMF)的活性代谢物霉酚酸(MPA)在肝移植病人体内的药代动力学。方法38例肝移植病人(男30例，女8例)术后早期按推荐剂量(每次1.0 g，每天两次)口服MMF达稳态，在给予一个早晨的剂量(1.0 g)后，在1个给药间隔内，于给药前及给药后不同时间点采血，用HPLC法测定MPA血药浓度，用3P97软件计算药代动力学参数。结果病人口服MMF后，血浆MPA浓度在给药后0.5～6.0 h内达峰值，部分病人在给药后4～12 h出现第2个小峰，血药峰浓度(C_max)和药-时曲线下面积(AUC_{0-12 h})均值分别为(12±7) μg·mL^-1和(44±16) μg·h·mL^-1，病人个体间存在较大差异。结论MPA在肝移植病人体内的药代动力学存在较大个体差异，提示在临床用药时需要监测MPA血药浓度，进行个体化给药。