Effect of coadministered lopinavir and ritonavir (Kaletra) on tacrolimus blood concentration in liver transplantation patients
Effect of coadministered lopinavir and ritonavir (Kaletra) on tacrolimus blood concentration in liver transplantation patients
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DOI：
10.1053/jlts.2003.50171
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发表时间：
2003-09-01
影响因子：
4.6
通讯作者：
Fung, JJ
中科院分区：
文献类型：
--
作者：
Jain, AB;Venkataramanan, R;Fung, JJ
随着高效抗逆转录病毒疗法（HAART）的出现，HIV阳性不再是肝移植的禁忌症。一些抗逆转录病毒剂，特别是蛋白酶抑制剂（例如，利托那韦、茚地那韦和奈非那韦）已被描述为某些免疫抑制药物代谢的有效抑制剂。在这篇文章中，我们描述了他克莫司和Kaletra（雅培实验室，芝加哥，IL）（洛匹那韦和利托那韦的组合）之间的深刻的相互作用在3例肝移植患者。患者1维持5 mg每日两次剂量的他克莫司，血药谷浓度约为10.6 ng/mL，在添加Kaletra后每周仅需0.5 mg他克莫司即可达到相似的他克莫司血药浓度，半衰期为10.6天。在患者2中，添加Kaletra后，他克莫司的血药浓度-时间曲线下面积从31 ng/mL/h增加至301 ng/mL/h，相应的半衰期为20天。当患者随后转换为奈非那韦时，半衰期缩短至10.3天。患者3在接受Kaletra前维持4 - 8 mg/d他克莫司治疗，相应的血药浓度为10 ng/mL，需要他克莫司剂量为1 mg/wk，他克莫司浓度为5 ng/mL。总之，洛匹那韦和利托那韦联合使用比使用单一蛋白酶抑制剂奈非那韦导致他克莫司血药浓度更显著增加。他克莫司剂量小于1 mg/wk可能足以维持Kaletra患者足够的血药浓度。患者可能不需要进一步剂量的他克莫司3至5周取决于肝功能时，开始治疗Kaletra。在肝移植后HIV阳性患者中，特别是在存在肝功能障碍的情况下，当引入或停用Kaletra时，需要非常谨慎地管理他克莫司剂量。
With the advent of highly active antiretroviral therapy (HAART), HIV positivity is no longer a contraindication for liver transplantation. Some of the antiretroviral agents, particularly protease inhibitors (e.g., ritonavir, indinavir, and nelfinavir) have been described as potent inhibitors of the metabolism of certain immunosuppressive drugs. In this article we describe a profound interaction between tacrolimus and Kaletra (Abbott Laboratories, Chicago, IL) (a combination of lopinavir and ritonavir) in 3 liver transplantation patients. Patient 1, who was maintained on a 5 mg twice daily dose of tacrolimus with a trough blood concentration around 10.6 ng/mL, required only 0.5 mg of tacrolimus per week after addition of Kaletra to achieve similar tacrolimus blood concentrations, with a half-life of 10.6 days. In patient 2, the area under the blood concentration versus time curve for tacrolimus increased from 31 ng/mL/h to 301 ng/mL/h after addition of Kaletra, with a corresponding half-life of 20 days. When the patient was subsequently switched to nelfinavir, the half-life decreased to 10.3 days. Patient 3, who was maintained with 4 to 8 mg/d of tacrolimus and a corresponding blood concentration of 10 ng/mL before Kaletra, required a tacrolimus dose of 1 mg/wk and tacrolimus; concentrations of 5 ng/mL with Kaletra. In conclusion, a combination of lopinavir and ritonavir led to a much more profound increase in tacrolimus blood concentrations than use of single protease inhibitor, nelfinavir. A tacrolimus dose of less than 1 mg/wk may be sufficient to maintain adequate blood tacrolimus concentrations in patients on Kaletra. Patients may not need a further dose of tacrolimus for 3 to 5 weeks depending on liver function when therapy with Kaletra is initiated. Great caution is required in the management of tacrolimus dosage when Kaletra is introduced or withdrawn in HIV-positive patients after liver transplantation, particularly in the presence of hepatic dysfunction.