González-Roncero F M, Govantes M A G, Chaves V C, Palomo P P, Serra M B
Servicio de Nefrologia, Hospitales Universitarios Virgen del Rocio, Sevilla, Spain.
Transplant Proc. 2007 Sep;39(7):2176-8. doi: 10.1016/j.transproceed.2007.06.063.
The acyl glucuronide of mycophenolic acid (AcMPAG) is a metabolite with in vitro immunosuppressive activity. The chemical properties of acyl glucuronides have been associated with the toxicity of some drugs. The aim of our study was to analyze the influence of renal insufficiency on the pharmacokinetics of AcMPAG. Areas under the 12-hour curve (AUC(0-12h)) of MPA, glucuronide of MPA (MPAG), and AcMPAG were determined by high performance liquid chromatography performed in 20 renal transplantation patients under treatment with mycophenolate mofetil (MMF), cyclosporine, and steroids. They were divided between a group with preserved renal function (group I, mean creatinine clearance [Clcr] of 105 +/- 7 mL/min) and one with advanced renal insufficiency (group II, mean Clcr of 27 +/- 5 mL/min). There was no difference in MMF dose or MPA-AUC(0-12h) values between groups. Mean predose levels of AcMPAG-C0 and AcMPAG-AUC(0-12h) were much higher in group II than in group I (0.5 +/- 2 vs 1.6 +/- 1 microg/mL and 12 +/- 2 vs. 32 +/- 19 microg*h/mL respectively, P < .005). The present data suggested that AcMPAG, a metabolite with immunosuppressive activity that may be related to toxic effects of MPA, is renally eliminated. Its levels can significantly rise in patients with renal insufficiency. Although further studies with more patients are required to determine the role of AcMPAG in MPA toxicity, we believe that this accumulation may be of clinical relevance.
霉酚酸的酰基葡萄糖醛酸化物（AcMPAG）是一种具有体外免疫抑制活性的代谢产物。酰基葡萄糖醛酸化物的化学性质与某些药物的毒性有关。我们研究的目的是分析肾功能不全对AcMPAG药代动力学的影响。通过高效液相色谱法测定了20例接受霉酚酸酯（MMF）、环孢素和类固醇治疗的肾移植患者体内霉酚酸（MPA）、MPA的葡萄糖醛酸化物（MPAG）和AcMPAG的12小时曲线下面积（AUC(0 - 12h)）。他们被分为肾功能保留组（I组，平均肌酐清除率[Clcr]为105±7 mL/min）和重度肾功能不全组（II组，平均Clcr为27±5 mL/min）。两组之间MMF剂量或MPA - AUC(0 - 12h)值没有差异。II组中AcMPAG - C0和AcMPAG - AUC(0 - 12h)的平均给药前水平显著高于I组（分别为0.5±2 vs 1.6±1 microg/mL和12±2 vs 32±19 microg*h/mL，P <.005）。目前的数据表明，具有免疫抑制活性且可能与MPA毒性作用相关的代谢产物AcMPAG经肾脏排泄。其水平在肾功能不全患者中可显著升高。尽管需要更多患者参与进一步研究以确定AcMPAG在MPA毒性中的作用，但我们认为这种蓄积可能具有临床意义。
