Pharmacokinetic booster simulation of ritonavir improves the benefits of lopinavir for virtual patients with COVID-19

The coronavirus disease 2019 (COVID-19) pandemic and its persistence have created a need for effective treatments. Patients with COVID-19 have been treated with a combinatorial therapy comprising lopinavir and ritonavir (LPV/r), which is used to treat human immunodeficiency virus infection. However, the results of an open-label randomized controlled trial led to the removal of this modality from the list of recommended agents in the Japanese COVID-19 Treatment Guide. We believe that an insufficient dose of LPV/r caused the lack of therapeutic effect. Therefore, based on previous models, we quantitatively evaluated whether adequate amounts of the pharmacokinetic booster LPV/r could modulate LPV clearance. Our results showed that the strategy of increasing the dose of LPV/r improved the safety and efficacy of the treatment. Thus, owing to the fact that it increased the LPV concentration, the pharmacokinetic booster LPV/r may serve as a potential therapeutic for COVID-19.