Vasquez E M, Pollak R
Department of Pharmacy Practice, University of Illinois at Chicago 60612, USA.
Clin Transplant. 1997 Feb;11(1):38-41.
Numerous drugs have been reported to alter cyclosporine (CSA) blood levels, most notably, those drugs that interfere with cytochrome P450 metabolism. Our clinical experience suggested that OKT3 therapy may alter CSA blood levels as well. The purpose of this study was to assess the effect of OKT3 therapy on CSA trough blood levels. We reviewed medical records of all CSA-treated renal transplant recipients during a 3-yr period to identify patients who received antilymphocyte induction therapy. Patients receiving drugs known to interact with CSA were excluded from analysis. The study population (n = 33) was divided into two groups: the OKT3 group consisting of 17 patients who received OKT3 therapy for 7 d post-transplant (OKT3 group) and the control consisting of 16 patients who received ALG induction therapy for 7 d post-transplant (ALG group). Oral CSA (14 mg/kg) was administered preoperatively. Postoperatively, oral CSA (4 mg/kg) was administered twice daily, in addition to corticosteroids and azathioprine. We evaluated CSA through levels on days 1, 3, 5, and 7 of antilymphocyte therapy and 3 d following completion of antilymphocyte therapy. On days 1 and 3, CSA trough levels did not differ between the two groups. However, median CSA trough levels (HPLC) were significantly higher among OKT3-treated patients on day 5 of therapy (265 ng/ml), as compared to ALG-treated patients (136 ng/ml; p < 0.0001; Mann-Whitney U-test). On days 7 and 10, CSA trough levels did not differ between the two groups. CSA does, however, had been adjusted based on levels obtained on day 5. We conclude that OKT3 therapy causes a significant rise in CSA trough levels. Recognition of this potential drug interaction is essential in titrating CSA doses in the early post-transplant period to minimize risks of CSA toxicity or early rejection following induction therapy.
据报道，许多药物会改变环孢素（CSA）的血药浓度，其中最显著的是那些干扰细胞色素P450代谢的药物。我们的临床经验表明，OKT3治疗也可能改变CSA血药浓度。本研究的目的是评估OKT3治疗对CSA谷血药浓度的影响。我们回顾了3年期间所有接受CSA治疗的肾移植受者的病历，以确定接受抗淋巴细胞诱导治疗的患者。接受已知与CSA相互作用药物治疗的患者被排除在分析之外。研究人群（n = 33）分为两组：OKT3组由17例移植后接受7天OKT3治疗的患者组成（OKT3组），对照组由16例移植后接受7天抗淋巴细胞球蛋白（ALG）诱导治疗的患者组成（ALG组）。术前口服CSA（14 mg/kg）。术后，除皮质类固醇和硫唑嘌呤外，口服CSA（4 mg/kg），每日两次。我们在抗淋巴细胞治疗的第1、3、5和7天以及抗淋巴细胞治疗完成后3天评估CSA血药浓度。在第1天和第3天，两组间CSA谷浓度无差异。然而，在治疗第5天，OKT3治疗的患者中CSA谷浓度中位数（高效液相色谱法）显著高于ALG治疗的患者（265 ng/ml比136 ng/ml；p < 0.0001；曼-惠特尼U检验）。在第7天和第10天，两组间CSA谷浓度无差异。不过，CSA已根据第5天测得的浓度进行了调整。我们得出结论，OKT3治疗会导致CSA谷浓度显著升高。认识到这种潜在的药物相互作用对于在移植后早期调整CSA剂量以将诱导治疗后CSA毒性或早期排斥反应的风险降至最低至关重要。
