Plasma Concentrations and Safety of Lopinavir/ritonavir in COVID-19 Patients A Short Communication.

Background Although the efficacy of lopinavir/ritonavir has not been proven, it has been proposed as an off-label treatment for COVID-19. Previously, it has been reported that the plasma concentrations of lopinavir significantly increase in inflammatory settings. As COVID-19 may be associated with major inflammation, assessing the plasma concentrations and safety of lopinavir in COVID-19 patients is essential. Methods Real-world COVID-19 data based on a retrospective study. Results Among the 31 COVID-19 patients treated with lopinavir/ritonavir between March 18, 2020 and April 1, 2020, it was observed higher lopinavir plasma concentrations, which increased by 4.6-fold (interquartile range: 3.6-6.2), as compared to the average plasma concentrations in HIV. Lopinavir concentrations in all except one patient were above the upper limit of the concentration range of HIV treatment. Approximately one to five patients prematurely stopped treatment mainly due to an ADR related to hepatic or gastrointestinal disorders. Conclusion Lopinavir plasma concentrations in patients with moderate to severe COVID-19 were higher than expected, and they were associated with the occurrence of hepatic or gastrointestinal adverse drug reactions. However, a high plasma concentration may be required for in vivo antiviral activity against SARS-CoV-2, as suggested by previous studies. Therefore, in the absence of adverse drug reaction, lopinavir dosage should not be reduced. Cautionu is essential because off-label use can be associated with a new drug safety profile.