Department of Clinical Pharmacology, Basil Hetzel Institute, The Queen Elizabeth Hospital, Woodville South, SA, 5011, Australia.
Discipline of Pharmacology, Adelaide Medical School, University of Adelaide, Adelaide, SA, 5000, Australia.
Br J Clin Pharmacol. 2019 May;85(5):1015-1020. doi: 10.1111/bcp.13880. Epub 2019 Mar 6.
The immunosuppressant cyclosporin is a P-glycoprotein (P-gp) substrate whose impaired function has been associated with an increased risk of cyclosporin-induced nephrotoxicity following renal transplantation. This study investigated the relationship between blood and allograft cyclosporin concentration, and the effect of P-gp expression. Fifty biopsy samples were obtained from 39 renal transplant recipients who received cyclosporin as part of maintenance immunosuppression. Blood cyclosporin concentrations (2 hours postdose) were obtained from clinical records, matching allograft cyclosporin concentrations were measured in frozen biopsy tissue by liquid chromatography-tandem mass spectrometry, and allograft P-gp expression was assessed by immunohistochemistry. Blood and allograft cyclosporin concentrations in the 1st month post-transplantation ranged from 505-2005 μg/L and 0.01-16.7 ng/mg tissue, respectively. Dose was the only significant predictor of allograft cyclosporin concentrations (adjusted R = .24, F-statistic = 11.52, P = .0019), with no effect of P-gp expression or blood cyclosporin concentrations. P-gp expression is not the major determinant of allograft cyclosporin concentrations.
免疫抑制剂环孢素是一种 P 糖蛋白（P-gp）底物，其功能受损与肾移植后环孢素诱导的肾毒性风险增加有关。本研究调查了血药浓度和移植物中环孢素浓度之间的关系，以及 P-gp 表达的影响。本研究纳入 39 例接受环孢素作为维持性免疫抑制治疗的肾移植受者，获取了 50 例活检样本。从临床记录中获取血药浓度（给药后 2 小时），采用液相色谱-串联质谱法测定冷冻活检组织中的移植物中环孢素浓度，并用免疫组织化学法评估移植物 P-gp 表达。移植后 1 个月内，血药和移植物中环孢素浓度范围分别为 505-2005μg/L 和 0.01-16.7ng/mg 组织。剂量是唯一显著预测移植物中环孢素浓度的因素（调整 R ² =.24，F 统计量 = 11.52，P = .0019），P-gp 表达或血药浓度无影响。P-gp 表达不是移植物中环孢素浓度的主要决定因素。
