Lopinavir/ritonavir (LPV/RTV)

population PBPK/PD

Lopinavir-ritonavir did not show promise for treatment of hospitalized COVID-19 patients with pneumonia in a recent clinical trial in China, but this trial was underpowered. Lopinavir-ritonavir is under investigation in a World Health Organization study.

For lopinavir, in the absence of human serum, the EC50 against HIV-1 ranges from 0.006 – 0.017 µg/mL, whereas in the presence of 50% human serum, the EC50 is approximately 10-fold higher (0.04 – 0.18 mcg/mL), representing the significant impact of plasma protein binding on potency. While published reports for SARS-CoV-2 are not available, in vitro potency for related coronaviruses are assumed to be similar. The published IC50s or EC50s in the absence of human serum (ie, unbound drug) for LPV for SARS or and MERS viruses has been reported to range from 4 to 15 µg/mL (See Supplementary Materials). The in vitro potency of LPV against coronaviruses would suggest that LPV may be more than 100 times less active against SARS-CoV-2 compared to HIV-1. Therefore, higher drug exposures and possibly a new dose regimen may be required to successfully treat coronaviruses with LPV/r.

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