The results clearly indicate that drug metabolism enzymes (cytochrome P450 3A) are inhibited by systemic inflammation. “Caution is advised when prescribing CYP3A4 substrates such as Lopinavir/Ritonavir or any other drug with a narrow therapeutic index to Covid-19 patients because of the risk of elevated drug levels and related toxicities.”
Importantly, from the Lopinavir and Hydroxychloroquine concentrations in the plasma, the study group calculated the corresponding concentration in the lung compartment – the anatomic site of SARS-CoV-2 infection. The results strongly suggest that it is unlikely that both drugs reach sufficient concentrations to inhibit the virus replication in the lung.
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