Wigger Marianne, Armstrong Victor William, Shipkova Maria, Wacke Rainer, Nizze Horst, Streit Frank, von Ahsen Nicolas, Muscheites Jutta, Glasenapp Sabine, Stolpe Hans-Joachim, Oellerich Michael
Department for Pediatric Nephrology and Dialysis, University of Rostock, Rostock, Germany.
Ther Drug Monit. 2002 Jun;24(3):438-43. doi: 10.1097/00007691-200206000-00019.
A juvenile, female renal transplant recipient suffered two acute rejection episodes: the first on posttransplant day 31 while taking cyclosporine, prednisone, and mycophenolate mofetil (MMF); and the second on posttransplant day 67, when she was taking tacrolimus, prednisone, and MMF. Dosage of MMF was initially started at 2 g/d (corresponding to 600 mg MMF/m(2) twice daily.), but was reduced to 250 mg/d to 500 mg/d after severe diarrhea and a paralytic ileus on posttransplant day 16. During therapy with tacrolimus, prednisone, and MMF, predose plasma mycophenolic acid (MPA) concentrations varied from 1.1 mg/L to 8.2 mg/L (median 3.0 mg/L). On posttransplant day 91, a 12-hour pharmacokinetic profile was obtained. The concentrations of MPA and its metabolites were determined with a validated high-performance liquid chromatography (HPLC) procedure. After oral MMF (250 mg) administration, the MPA concentration showed an atypical decline from a predose concentration of 6.0 mg/L to a value of 3.8 mg/L at 75 minutes postdose, and 3.4 mg/L at 6 hours postdose, before returning to 6.0 mg/L after 12 hours. The 12-hour area under the concentration-time curve (AUC) values for MPA and its major metabolite the phenolic glucuronide MPAG were 55.1 mg.h/L and 800 mg.h/L, respectively. An unusually high concentration (12-h AUC, 165 mg.h/L) of the phenolic glucose conjugate of MPA was found. The apparent renal clearance of MPAG was only 2.2 mL/min. Her creatinine clearance was 30 mL/min. MPAG clearances have been reported to range from approximately. 5.5 mL/min to 35 mL/min at a creatinine clearance of approximately 30 mL/min in renal transplant recipients. The authors' findings suggest that conjugation and clearance of MPA through the kidney is strongly impaired in this patient. The relatively high predose MPA concentrations could result from an enhanced enterohepatic circulation of MPA and its metabolites.
第一次在移植后第31天，当时正在服用环孢素、泼尼松和霉酚酸酯（MMF）；第二次在移植后第67天，此时她正在服用他克莫司、泼尼松和MMF。MMF的剂量最初起始为2 g/d（相当于600 mg MMF/m²，每日两次），但在移植后第16天出现严重腹泻和麻痹性肠梗阻后，剂量减至250 mg/d至500 mg/d。在用他克莫司、泼尼松和MMF治疗期间，给药前血浆霉酚酸（MPA）浓度在1.1 mg/L至8.2 mg/L之间变化（中位数为3.0 mg/L）。在移植后第91天，获得了一份12小时的药代动力学曲线。MPA及其代谢物的浓度通过经过验证的高效液相色谱（HPLC）方法测定。口服MMF（250 mg）后，MPA浓度呈现非典型下降，给药前浓度为6.0 mg/L，给药后75分钟降至3.8 mg/L，给药后6小时降至3.4 mg/L，12小时后又回到6.0 mg/L。MPA及其主要代谢物酚葡糖苷酸MPAG的12小时浓度-时间曲线下面积（AUC）值分别为55.1 mg·h/L和800 mg·h/L。发现MPA的酚葡萄糖共轭物浓度异常高（12小时AUC，165 mg·h/L）。MPAG的表观肾清除率仅为2.2 mL/min。她的肌酐清除率为30 mL/min。据报道，在肾移植受者肌酐清除率约为30 mL/min时，MPAG清除率范围约为5.5 mL/min至35 mL/min。作者的研究结果表明，该患者中MPA通过肾脏的共轭和清除严重受损。给药前MPA浓度相对较高可能是由于MPA及其代谢物的肠肝循环增强所致。
Zotero 插件