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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Effect of calcineurin inhibitor therapy on P-gp expression and function in lymphocytes of renal transplant patients: a preliminary evaluation.
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Effect of calcineurin inhibitor therapy on P-gp expression and function in lymphocytes of renal transplant patients: a preliminary evaluation.

机译：钙调神经磷酸酶抑制剂治疗对肾移植患者淋巴细胞中P-gp表达和功能的影响：初步评估。

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摘要

Cyclosporine and tacrolimus are substrates and potent inhibitors of the multidrug transporter, P-glycoprotein, in vitro. The authors have investigated the effect of chronic therapy with these and other immunosuppressive drugs on the expression and function of P-glycoprotein in T lymphocytes. Using a P-gp antibody, the authors studied the level of expression of P-gp in CD4 and CD8 T cells over a period of time in renal transplant patients. For comparison, a group of healthy volunteers and patients who did not receive any calcineurin inhibitors but were maintained on mycophenolate mofetil was included. The P-gp expression on lymphocytes from these two groups remained constant (over several months' time). However, patients who were started on tacrolimus or cyclosporine had an initial decline in expression of P-gp on CD4 T cells. Patients who were initiated on calcineurin therapy on day 1 posttransplant also had a decrease in expression of P-gp on CD4 T lymphocytes. This preliminary analysis suggests that the calcineurin inhibitors might be modulating the expression and function of transporters in lymphocytes, thus changing not only the drug concentration but also the apparent efficacy of these drugs. Further understanding and elucidation of such effects would be important in understanding the relationship between pharmacokinetics and pharmacodynamics of these and other drugs, especially for immunosuppressive and anti-AIDS therapy.
机译：环孢菌素和他克莫司是体外多药转运蛋白P-糖蛋白的底物和有效抑制剂。作者研究了使用这些和其他免疫抑制药物进行长期治疗对T淋巴细胞中P-糖蛋白表达和功能的影响。作者使用P-gp抗体研究了肾移植患者一段时间内CD4和CD8 T细胞中P-gp的表达水平。为了进行比较，包括一组健康志愿者和未接受钙调神经磷酸酶抑制剂但仍接受霉酚酸酯治疗的患者。两组淋巴细胞上的P-gp表达保持恒定（几个月后）。但是，开始使用他克莫司或环孢霉素的患者在CD4 T细胞上的P-gp表达最初有所下降。在移植后第1天开始接受钙调神经磷酸酶治疗的患者，CD4 T淋巴细胞上P-gp的表达也下降。这项初步分析表明，钙调神经磷酸酶抑制剂可能正在调节淋巴细胞中转运蛋白的表达和功能，从而不仅改变药物浓度，而且改变这些药物的表观功效。进一步了解和阐明这种作用对于理解这些药物和其他药物的药代动力学和药效学之间的关系非常重要，特别是对于免疫抑制和抗艾滋病治疗而言。

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