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MeSH Disease

COVID-19 (1)


HGNC Genes

SARS-CoV-2 proteins

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    Effect of Systemic Inflammatory Response to SARS-CoV-2 on Lopinavir and Hydroxychloroquine Plasma Concentrations

    Authors: Catia Marzolini; Felix Stader; Marcel Stoeckle; Fabian Franzeck; Adrian Egli; Stefano Bassetti; Alexa Hollinger; Michael Osthoff; Maja Weisser; Eva Caroline Gebhard; Veronika Baettig; Julia Geenen; Nina Khanna; Sarah Tschudin-Sutter; Daniel Mueller; Hans Hirsch; Manuel Battegay; Parham Sendi

    doi:10.1101/2020.07.05.20146878 Date: 2020-07-07 Source: medRxiv

    Background: Coronavirus disease 2019 MESHD ( COVID-19 MESHD) leads to inflammatory cytokine release, which can downregulate the expression of metabolizing enzymes. This cascade affects drug concentrations in the plasma. We investigated the association between lopinavir (LPV) and hydroxychloroquine (HCQ) plasma concentrations and the values of acute phase inflammation marker C-reactive protein HGNC ( CRP HGNC). Methods: LPV plasma concentrations were prospectively collected in 92 patients hospitalized at our institution. Lopinavir/ritonavir was administered 12 hourly, 800/200 mg on day 1, and 400/100 mg on day 2 until day 5 or 7. HCQ was given at 800 mg, followed by 400 mg after 6, 24 and 48 hours. Hematological, liver, kidney, and inflammation laboratory values were analyzed on the day of drug level determination. Results: The median age of study participants was 59 (range 24 up to 85) years, and 71% were male. The median duration from symptom onset to hospitalization and treatment initiation was 7 days (IQR 4;10) and 8 days (IQR 5;10), respectively. The median LPV trough concentration on day 3 of treatment was 26.5 ug/mL (IQR 18.9;31.5). LPV plasma concentrations positively correlated with CRP HGNC values (r=0.37, p<0.001), and were significantly lower when tocilizumab was preadministrated. No correlation was found between HCQ concentrations and CRP HGNC values. Conclusions: High LPV plasma concentrations were observed in COVID-19 MESHD patients. The ratio of calculated unbound drug fraction to published SARS-CoV2 EC50 values indicated insufficient LPV concentrations in the lung. CRP HGNC values significantly correlated with LPV but not HCQ plasma concentrations, implying inhibition of cytochrome P450 3A4 HGNC ( CYP3A4 HGNC) metabolism by inflammation.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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