Paxlovid对肺移植患者他克莫司血药浓度影响的研究

Study on the effect of paxlovid on the plasma concentration of tacrolimus in patients with lung transplantation

目的探索奈玛特韦片/利托那韦片组合包装(Paxlovid)对肺移植患者他克莫司(Tacrolimus,TAC)血药浓度的影响,为肺移植术后的新型冠状病毒感染患者服用Paxlovid与TAC时的用药安全提供合理参考。方法回顾性分析2022年11月1日至2023年1月31日中日友好医院收治的5例肺移植术后服用Paxlovid的患者(服用Paxlovid之前,5例患者的TAC血药浓度均已达稳态),测定服用Paxlovid期间及之后的TAC谷浓度,记录Paxlovid停药后重新启用TAC的时间和剂量,同时收集用药期间患者的肝肾功能指标数据。结果在Paxlovid使用期间,3例患者的TAC血药浓度分别下降19.4%、8.4%、14.7%,另外2例分别升高了21.6%、80.6%。重新启用TAC之后,3例患者TAC谷浓度出现了先上升(平均上升59.5%)后下降(平均下降33.3%)的趋势,而另外2例患者TAC谷浓度则一直持续下降。4例患者分别是在TAC血药浓度为基线水平的47.2%、72.6%、83.8%、60.3%时开始恢复使用TAC,1例则是在基线水平的171.2%开始启用TAC。2例患者以基线剂量开始启用TAC,另外3例患者分别以85.7%、44.4%、90.9%的基线剂量开始重新使用。结论Paxlovid会对TAC血药浓度产生影响,不仅是在Paxlovid治疗期间,甚至持续至停药后第6天,存在显著的个体差异,建议在患者治疗期间严密监测TAC血药浓度,根据血药浓度实行个体化TAC给药方案。

Objective To explore the effect of paxlovid on the blood concentration of tacrolimus(TAC)used for a long time in patients after lung transplantation,so as to provide a reasonable reference for the drug safety of patients with COVID-19 after lung transplantation when taking paxlovid and TAC.Methods Five patients(Sino-Japanese Friendship Hospital,from November 1,2022 to January 31,2023)who took paxlovid after lung transplantation and whose TAC blood concentration had reached a steady state before that were retrospectively analyzed.The steady trough concentration of TAC during and after the use of paxlovid,and the time and dosage of re-adding TAC after the withdrawal of paxlovid were recorded.At the same time,the indexes of liver and kidney function of patients during the use of paxlovid were collected.Results During the use of Paxlovid,the TAC blood concentration in three patients decreased by 19.4%,8.4%,and 14.7%,respectively,while the other two patients increased by 21.6% and 80.6%,respectively.After re-adding TAC,the trough concentration of TAC in three patients increased(59.5% on average)and then decreased(33.3% on average),while the trough concentration of TAC in the other two patients declined continuou-sly.Four patients resumed using TAC at baseline concentrations of 47.2%,72.6%,83.8%,and 60.3%,respectively,while one patient started using TAC at baseline levels of 171.2%.Two patients started using TAC at baseline dosage,while the other three patients resumed using TAC at baseline dosage of 85.7%,44.4%,and 90.9%,respectively.Conclusion Paxlovid has a significant effect on the blood drug concentration of TAC.There is significant individual difference not only during the treatment of paxlovid,but even within 6 days after the drug withdrawal.It is suggested that the blood drug concentration of TAC should be closely monitored during the treatment,and the individualized TAC administration plan should be implemented according to the blood drug concentration.