与环孢素联合治疗相比，西罗莫司与霉酚酸联合使用时霉酚酸的暴露量更高。

Higher exposure to mycophenolic acid with sirolimus than with cyclosporine cotreatment.

作者信息

Büchler Matthias, Lebranchu Yvon, Bénéton Maud, Le Meur Yann, Heng Anne Elisabeth, Westeel Pierre François, le Guellec Chantal, Libert Frédéric, Hary Lionel, Marquet Pierre, Paintaud Gilles

机构信息

Department of Nephrology, Tours University Hospital, 37044 Tours, France.

出版信息

Clin Pharmacol Ther. 2005 Jul;78(1):34-42. doi: 10.1016/j.clpt.2005.03.005.

DOI:10.1016/j.clpt.2005.03.005

PMID:16003290

Abstract

INTRODUCTION

Therapeutic drug monitoring of mycophenolate mofetil is recommended because of the interindividual variability in the exposition to its active moiety, mycophenolic acid. However, most of the pharmacokinetic studies involved patients cotreated with cyclosporine (INN, ciclosporin).

METHODS

We analyzed the pharmacokinetics of mycophenolic acid in 13 renal graft recipients treated with sirolimus in an anticalcineurin-free regimen and compared it with that of 17 patients cotreated with cyclosporine. The area under the concentration versus time curve over a 12-hour period (AUC 0-12 ) of mycophenolic acid was estimated at 2 weeks, 1 month, 2 months, and 3 months after transplantation.

RESULTS

At the first 3 time points, patients cotreated with sirolimus had significantly higher mycophenolic acid AUC 0-12 values compared with patients cotreated with cyclosporine, as follows: 81 mg . h/L (SD, 39 mg . h/L) versus 43 mg . h/L (SD, 11 mg . h/L) (P < .001), 72 mg . h/L (SD, 17 mg . h/L) versus 48 mg . h/L (SD, 13 mg . h/L) (P < .001), and 70 mg . h/L (SD, 25 mg . h/L) versus 47 mg . h/L (SD, 17 mg . h/L) (P < .01) at week 2, month 1, and month 2, respectively. At all time points, patients cotreated with sirolimus had significantly higher dose-normalized mycophenolic acid AUC 0-12 values. At months 1 and 2, white blood cell counts were lower in the sirolimus group than in the cyclosporine group, as follows: 4.8 x 10(3)/mL (SD, 1.1 x 10(3)/mL) versus 6.5 x 10(3)/mL (SD, 2.2 x 10(3)/mL) (P < .01) at month 1 and 4.6 x 10(3)/mL (SD, 1.1 x 10(3)/mL) versus 5.9 x 10(3)/mL (SD, 2.0 x 10(3)/mL) (P < .05) at month 2.

CONCLUSION

These data show that exposure to mycophenolic acid is higher in patients cotreated with sirolimus than in those cotreated with cyclosporine.

摘要

引言

由于霉酚酸酯的活性成分霉酚酸在个体间存在暴露差异，因此推荐进行霉酚酸酯的治疗药物监测。然而，大多数药代动力学研究涉及与环孢素（国际非专利药品名称，环孢菌素）联合治疗的患者。

方法

我们分析了13例接受西罗莫司治疗且未使用钙调神经磷酸酶抑制剂方案的肾移植受者中霉酚酸的药代动力学，并将其与17例接受环孢素联合治疗的患者进行比较。在移植后2周、1个月、2个月和3个月时，估算霉酚酸在12小时内的浓度-时间曲线下面积（AUC₀₋₁₂）。

结果

在最初3个时间点，接受西罗莫司联合治疗的患者霉酚酸AUC₀₋₁₂值显著高于接受环孢素联合治疗的患者，具体如下：在第2周、第1个月和第2个月时，分别为81mg·h/L（标准差，39mg·h/L）对43mg·h/L（标准差，11mg·h/L）（P<.001）、72mg·h/L（标准差，17mg·h/L）对48mg·h/L（标准差，13mg·h/L）（P<.001）以及70mg·h/L（标准差，25mg·h/L）对47mg·h/L（标准差，17mg·h/L）（P<.01）。在所有时间点，接受西罗莫司联合治疗的患者剂量标准化的霉酚酸AUC₀₋₁₂值均显著更高。在第1个月和第2个月时，西罗莫司组的白细胞计数低于环孢素组，具体如下：在第1个月时，4.8×10³/mL（标准差，1.1×10³/mL）对6.5×10³/mL（标准差，2.2×10³/mL）（P<.01）；在第2个月时，4.6×10³/mL（标准差，1.1×10³/mL）对5.9×10³/mL（标准差，2.0×10³/mL）（P<.05）。