Pretransplantation Pharmacokinetic Curves of Tacrolimus in HIV-Infected Patients on Ritonavir-Containing cART: A Pilot Study
Pretransplantation Pharmacokinetic Curves of Tacrolimus in HIV-Infected Patients on Ritonavir-Containing cART: A Pilot Study
复制标题
DOI：
10.1097/tp.0b013e3182734651
复制
发表时间：
2013-01-27
期刊：
影响因子：
6.2
通讯作者：
van Zuilen, Arjan D.
中科院分区：
文献类型：
--
作者：
van Maarseveen, Erik M.;Crommelin, Heleen A.;van Zuilen, Arjan D.
背景。利托那韦是一种极强的P450细胞色素3A抑制剂，P450细胞色素3A是他克莫司的主要代谢酶。随后，他克莫司的药代动力学在很大程度上受到利托那韦在hiv感染移植受者中的联合施用的影响。因此，为防止hiv感染者移植后直接过度暴露于含利托那韦的cART，探讨他克莫司移植前药代动力学曲线的预测价值。在这些患者中建立了移植前他克莫司的药代动力学模型，并为每个患者建立了移植后的剂量建议。将药代动力学种群参数与hiv阴性患者进行比较，并评估移植手术后患者移植前曲线的预测价值。模型预测的移植后24 h他克莫司水平与实际的移植后24 h他克莫司水平无显著差异（14.6 vs. 17.8 ng/mL， P=0.19）。由于模拟的药代动力学曲线每12小时缺乏一个吸收峰，当达到相似的低谷水平时，平均12小时AUC比hiv阴性受体报告的AUC低约40%。总之，他克莫司的移植前曲线似乎是一种很有前途的工具，可以防止移植后使用利托那韦的cART患者直接过度暴露，并建议提高最低水平以达到与hiv阴性受体相当的暴露。
Background. Ritonavir is an extremely strong inhibitor of P450 cytochrome 3A, which is the main metabolizing enzyme of tacrolimus. Subsequently, the pharmacokinetics of tacrolimus are affected to a large extend by the coadministration of ritonavir in HIV-infected transplant recipients. Therefore, to prevent overexposure directly posttransplantation in HIV-infected patients on ritonavir-containing cART, the predictive value of a pretransplantation pharmacokinetic curve of tacrolimus was explored.Methods. A pretransplantation pharmacokinetic model of tacrolimus in these patients was developed, and a posttransplantation dosing advice was established for each individual patient. The pharmacokinetic population parameters were compared with HIV-negative patients, and predictive value of the pretransplantation curves was assessed in patients after the transplantation procedure.Results. No significant difference was found between the model-predicted and actual posttransplantation 24 h-tacrolimus levels (14.6 vs. 17.8 ng/mL, P=0.19). As the simulated pharmacokinetic curves lacked an absorption peak every 12 h, the mean 12 h-AUC was approximately 40 % lower compared with AUC's reported in HIV-negative recipients, when similar trough levels were targeted.Conclusion. In conclusion, pretransplantation curves of tacrolimus seem a promising tool to prevent overexposure directly posttransplantation in patients on ritonavir-containing cART and raising trough levels to achieve an exposure equivalent to HIV-negative recipients is suggested.