1 Department of Medicine and Clinical Research Center, University of California, San Francisco, CA. 2 Department of Surgery, University of California, San Francisco, CA. 3 EMMES, Bethesda, MD. 4 Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA. 5 Address correspondence to: Leslie Z. Benet, Ph.D., UCSF Box 0912, San Francisco, CA 94143-0912.
Transplantation. 2014 Mar 27;97(6):702-7. doi: 10.1097/01.TP.0000441097.30094.31.
Interactions between antiretrovirals (ARVs) and transplant immunosuppressant agents (IS) among HIV-infected transplant recipients may lead to lack of efficacy or toxicity. In transplant recipients not infected with HIV, tacrolimus (TAC) trough levels (C0) or cyclosporine (CsA) drawn at C0 or 2 hours after dosing (C2) correlate with drug exposure (area under the curve [AUC]/dose) and outcomes. Because of ARV-IS interactions in HIV-infected individuals, and the high rate of rejection in these subjects, this study investigated the correlations between IS concentrations and exposure to determine the best method to monitor immunosuppressant levels.
This study prospectively studied 50 HIV-infected transplant recipients undergoing kidney or liver transplantation evaluating the pharmacokinetics of the IS in 150 studies over time after transplantation (weeks 2 to 4, 12, 28, 52, and 104). IS levels were measured with liquid chromatography-tandem mass spectrometry and AUC calculated using WinNonlin 9.0. Correlation analyses were run on SAS 9.2.
CsA concentration at C4 correlated better with AUC than C0 or C2, and over time TAC concentration correlated better at C0 or C2.
It is suggested that C0 is acceptable for TAC monitoring, but poor predictability will occur at C0 with CsA. The low correlation of C0 with CsA AUC could be responsible for the higher rejection rates on CsA that has been reported in these subjects.
在感染 HIV 的移植受者中，抗逆转录病毒药物 (ARV) 与移植免疫抑制剂 (IS) 之间的相互作用可能导致疗效缺乏或毒性。在未感染 HIV 的移植受者中，他克莫司（TAC）谷浓度（C0）或环孢素（CsA）在给药后 C0 或 2 小时（C2）时的浓度与药物暴露（曲线下面积 [AUC]/剂量）和结果相关。由于 HIV 感染者中存在 ARV-IS 相互作用，以及这些受试者中排斥反应的发生率较高，本研究调查了 IS 浓度与暴露之间的相关性，以确定监测免疫抑制剂水平的最佳方法。
本研究前瞻性研究了 50 例接受肾或肝移植的 HIV 感染移植受者，评估了移植后 2 至 4 周、12 周、28 周、52 周和 104 周时 150 项研究中 IS 的药代动力学。使用液相色谱-串联质谱法测量 IS 水平，并使用 WinNonlin 9.0 计算 AUC。在 SAS 9.2 上运行相关分析。
C4 时的 CsA 浓度与 AUC 的相关性优于 C0 或 C2，而 TAC 浓度随着时间的推移在 C0 或 C2 时的相关性更好。
建议 C0 可用于 TAC 监测，但 C0 时 CsA 的预测性较差。C0 与 CsA AUC 的低相关性可能是导致这些受试者报告的 CsA 排斥率较高的原因。
