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Pharmacokinetic Simulation of Optimal Lopinavir and Ritonavir Dose Combination for COVID-19: Boosting Lopinavir With
Yuta Nakamaru1,2, Ken-Ichi Sako1, Naohito Ide1
1Department of Clinical Pharmacy, Nihon Pharmaceutical University, Saitama, Japan.
In Vivo (Athens, Greece)
|June 27, 2025
Summary
The standard dose of lopinavir (LPV) with ritonavir (r) is ineffective for COVID-19. A higher ritonavir dose (1,200 mg) with lopinavir (400 mg) may be optimal for treating COVID-19.
Area of Science:
- Pharmacology
- Infectious Diseases
- Drug Development
Background:
- Lopinavir/ritonavir (LPV/r) was repurposed for COVID-19 treatment.
- Clinical trials have not confirmed LPV/r efficacy for COVID-19.
- Current Japanese COVID-19 guidelines do not include LPV/r.
Purpose of the Study:
- To determine the optimal LPV/r dose combination for COVID-19 treatment.
- To investigate the pharmacokinetic relationship between LPV and ritonavir in COVID-19 patients.
Main Methods:
- Utilized maximum-effect models with data from healthy volunteers and HIV patients.
- Estimated LPV clearance based on ritonavir plasma concentration.
- Performed pharmacokinetic simulations using established modeling equations.
Main Results:
- The standard LPV/r dose (400 mg/100 mg twice daily) did not achieve optimal blood concentrations.
- Pharmacokinetic modeling suggests a higher ritonavir dose is needed.
- An optimal dose combination of 400 mg LPV with 1,200 mg ritonavir was estimated.
Conclusions:
- Ritonavir's booster effect on LPV in COVID-19 can be quantified.
- This study provides a basis for calculating an optimal LPV/r dose for COVID-19 treatment.
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