Background Lopinavir/ritonavir has been proposed as off-label treatment for Covid-19, although efficacy have not been proven. It has previously been shown that lopinavir plasma concentration is dramatically increased in inflammatory settings. As Covid-19 may be associated with major inflammation, assessing lopinavir plasma concentration and its safety in Covid-19 patients is essential. Methods Real-world Covid-19 experience based on a retrospective study. Results Of 31 patients treated by lopinavir/ritonavir for Covid-19, we observed very high lopinavir plasma concentrations, increased of 4.6-fold (IQR, 3.6-6.2) with regards to average plasma concentrations in HIV. All except one patient were above the upper limit of the concentration ranges of HIV treatment. About one over four to five patients prematurely stopped treatment mainly secondary an adverse drug reaction related to hepatic or gastrointestinal disorders. Conclusion Lopinavir plasma concentrations in patients with moderate to severe Covid-19 were higher than expected, associated with the occurrence of hepatic or gastrointestinal adverse drug reactions. However, owing that high plasma concentration may be required for in vivo antiviral activity against SARS-CoV-2 as suggested by previous studies, it appears that, in the absence of adverse drug reaction, lopinavir dosage should not be reduced. Cautious is necessary as off-label use can be associated with a new drug safety profile.

中文翻译：

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Covid-19患者的洛匹那韦/利托那韦的血浆浓度和安全性：简短交流

尽管尚未证实疗效，但已经提出将洛匹那韦/利托那韦用于Covid-19的脱标签治疗。先前已经显示，在炎性环境中洛匹那韦血浆浓度显着增加。由于Covid-19可能与主要炎症相关，因此评估lopinavir血浆浓度及其在Covid-19患者中的安全性至关重要。方法基于回顾性研究的真实Covid-19经验。结果在31例接受lopinavir / ritonavir治疗Covid-19的患者中，我们观察到非常高的lopinavir血浆浓度，相对于HIV的平均血浆浓度，升高了4.6倍（IQR，3.6-6.2）。除一名患者外，所有患者均超出HIV治疗浓度范围的上限。大约四到五分之一的患者过早停止治疗，主要是继发与肝或胃肠道疾病有关的药物不良反应。结论中度至重度Covid-19患者的洛匹那韦血浆浓度高于预期，与发生肝或胃肠道不良药物反应有关。然而，由于如先前研究所建议的，针对体内针对SARS-CoV-2的抗病毒活性可能需要高血浆浓度，因此，在没有药物不良反应的情况下，洛匹那韦的剂量不应减少。必须谨慎使用，因为标签外使用可能与新药物安全性相关。结论中度至重度Covid-19患者的洛匹那韦血浆浓度高于预期，与发生肝或胃肠道药物不良反应有关。然而，由于如先前研究所建议的，针对体内针对SARS-CoV-2的抗病毒活性可能需要高血浆浓度，因此，在没有药物不良反应的情况下，洛匹那韦的剂量不应减少。必须谨慎使用，因为标签外使用可能与新药物安全性相关。结论中度至重度Covid-19患者的洛匹那韦血浆浓度高于预期，与发生肝或胃肠道药物不良反应有关。然而，由于如先前研究所建议的，针对体内针对SARS-CoV-2的抗病毒活性可能需要高血浆浓度，因此，在没有药物不良反应的情况下，洛匹那韦的剂量不应减少。必须谨慎使用，因为标签外使用可能与新的药物安全性相关。洛匹那韦的剂量不应减少。必须谨慎使用，因为标签外使用可能与新的药物安全性相关。洛匹那韦的剂量不应减少。必须谨慎使用，因为标签外使用可能与新药物安全性相关。