Plasma Concentrations and Safety of Lopinavir/Ritonavir in COVID-19 Patients. Issue 1 (February 2021)

• Record Type: Journal Article
• Authors: Chouchana, Laurent; Boujaafar, Sana; Gana, Ines; Preta, Laure-Hélène; Regard, Lucile; Legendre, Paul; Azoulay, Celia; Canouï, Etienne; Zerbit, Jeremie; Carlier, Nicolas; Terrier, Benjamin; Kernéis, Solen; Batista, Rui; Treluyer, Jean-Marc; Zheng, Yi; Benaboud, Sihem
• Is Part Of: Therapeutic drug monitoring. Volume 43:Issue 1(2021)
• Page Start: 131
• Page End: 135
• Publication Date: 2021-02
• Subjects: COVID-19 -- SARS-CoV-2 -- plasma concentration -- lopinavir -- therapeutic drug monitoring -- drug safety; Pharmacokinetics -- Periodicals; Patient monitoring -- Periodicals; Drugs -- Analysis -- Periodicals; Body fluids -- Analysis -- Periodicals; Drug Therapy -- Periodicals; Monitoring, Physiologic -- Periodicals; Pharmacology -- Periodicals; 615.7
• DOI: 10.1097/FTD.0000000000000838
• Languages: English
• ISSNs: 0163-4356

Abstract

Abstract : 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, higher lopinavir plasma concentrations were observed, which increased by 4.6-fold (interquartile range: 3.6–6.2), compared with 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 5 patients prematurely stopped treatment mainly because of an ADR related to hepatic or gastrointestinal disorders. Conclusions: 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. Caution is essential because off-label use can be associated with a new drug safety profile.