ArticleIn vivo (Athens, Greece)
Pharmacokinetic Simulation of Optimal Lopinavir and Ritonavir Dose Combination for COVID-19: Boosting Lopinavir With Ritonavir.
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Abstract
BACKGROUND/
aimLopinavir (LPV) combined with ritonavir (LPV/r) was initially developed to treat human immunodeficiency virus (HIV) infection and was subsequently repurposed to treat coronavirus disease 2019 (COVID-19) during the COVID-19 pandemic. As the efficacy of LPV/r in COVID-19 treatment has not been confirmed in clinical trials, LPV/r is not included in the Japanese COVID-19 treatment guidelines. Furthermore, previous clinical studies have not demonstrated the benefit of LPV/r against COVID-19 when used at the same dose as that used to treat HIV infection. Therefore, the aim of this study was to determine the optimal LPV/r dose combination for COVID-19 treatment. PATIENTS AND
methodsBased on data from healthy volunteers and patients with HIV infection, maximum-effect models were used to estimate the relationship between LPV clearance and ritonavir plasma concentration. Pharmacokinetic simulations were performed using a range of assumptions based on previously reported modeling equations.
resultsThe standard LPV/r dose combination of 400 mg/100 mg twice daily did not yield optimal blood concentrations. Based on the pharmacokinetic booster effect of ritonavir, the estimated optimal dose combination was 400 mg LPV boosted with 1,200 mg ritonavir.
conclusionThese findings provide a basis to quantify the booster effect of ritonavir on LPV in COVID-19 treatment and calculate the optimal LPV and ritonavir dose combination.
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