Alexander Suceena, Fleming Denise H, Mathew Binu S, Varughese Santosh, Jeyaseelan Visalakshi, Tamilarasi Veerasamy, Jacob Chakko K, John George T
Departments of *Nephrology; †Clinical Pharmacology; ‡Biostatistics, Christian Medical College, Vellore, India; and §Department of Renal Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia.
Ther Drug Monit. 2014 Aug;36(4):423-32. doi: 10.1097/FTD.0000000000000031.
Mycophenolate mofetil (MMF) has variable pharmacokinetics. This study examines the pharmacokinetic and clinical correlations in proliferative lupus nephritis.
Thirty-four patients were started on MMF, and the area under the concentration-time curve (AUC) was measured by limited sampling strategies, and dosing was adjusted to achieve an AUC of 30-60 mg·h·L. Twenty-seven patients had at least 2 measurements, and renal response was assessed within 1 year.
About 61.8% of patients had mycophenolic acid (MPA) AUC <30 mg·h·L with an empiric starting dose of 30 mg/kg. About 79.4% of patients achieved renal response by 1 year, and the median time to renal response was 111 days. MMF dose per body weight had a weak correlation with the AUC and did not correlate with trough concentrations. The median dose was 1.5 g/d at entry and 2 g/d after dose modification during the induction phase. Trough concentrations had a weak correlation with AUC. Patients with serum albumin ≥35 g/L had a greater chance of having an AUC ≥30 mg·h·L. The between-patient coefficient of variability for dose-normalized AUC was 37.9% at entry and 31% within 1 year, whereas repeated measurements over time in an individual had a good intraclass correlation of 0.78. Infections occurred in 11.8% and toxicities in 5.9%. MPA exposure was not significantly associated with adverse events. Patients with an AUC ≥30 mg·h·L had greater renal response at 1 year.
Lupus nephritis patients induced with concentration-controlled MMF had excellent renal response and fewer adverse events with lower than usual dosing. MPA exposure had high interpatient variability, requiring measurements for personalized dosing, and fewer adverse events. Long-term cost reduction is achievable with lower doses and good renal response in the majority of patients.
霉酚酸酯（MMF）具有可变的药代动力学。本研究考察增殖性狼疮性肾炎患者的药代动力学与临床的相关性。
34例患者开始使用MMF，通过有限采样策略测定浓度-时间曲线下面积（AUC），并调整剂量以使AUC达到30 - 60mg·h·L。27例患者至少进行了2次测量，并在1年内评估肾脏反应。
经验性起始剂量为30mg/kg时，约61.8%的患者霉酚酸（MPA）AUC <30mg·h·L。约79.4%的患者在1年内实现肾脏反应，肾脏反应的中位时间为111天。MMF每体重剂量与AUC呈弱相关，与谷浓度无相关性。诱导期开始时的中位剂量为1.5g/d，剂量调整后为2g/d。谷浓度与AUC呈弱相关。血清白蛋白≥35g/L的患者AUC≥30mg·h·L的可能性更大。剂量标准化AUC的患者间变异系数在开始时为37.9%，1年内为31%，而个体随时间的重复测量具有良好的组内相关性0.78。感染发生率为11.8%，毒性反应发生率为5.9%。MPA暴露与不良事件无显著相关性。AUC≥30mg·h·L的患者在1年时肾脏反应更佳。
采用浓度控制的MMF诱导治疗的狼疮性肾炎患者具有良好的肾脏反应，不良事件较少，且给药剂量低于常规剂量。MPA暴露在患者间具有高度变异性，需要进行测量以实现个体化给药，不良事件较少。通过较低剂量和大多数患者良好的肾脏反应可实现长期成本降低。
