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Related Experiment Video

Updated: Sep 17, 2025

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

Long-acting Injectable Containing Lopinavir Eliminates Reliance on Ritonavir Pharmacokinetic Enhancement.

Simone Perazzolo¹, Charles W Flexner², Zachary R Stephen¹

¹Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.

The Journal of Infectious Diseases

|June 27, 2025

Summary

This summary is machine-generated.

Ritonavir may not be needed in long-acting injectable protease inhibitor formulations. Lopinavir showed extended persistence, suggesting potential for reduced side effects and drug interactions in HIV and COVID-19 treatments.

Keywords:

boosting injectables long acting protease inhibitors ritonavir

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Area of Science:

Pharmacology
Drug Delivery
Infectious Diseases

Background:

Protease inhibitors, crucial for HIV and COVID-19 treatment, often require ritonavir to boost bioavailability by inhibiting first-pass metabolism.
Current long-acting injectable formulations aim to improve patient adherence and drug efficacy.

Purpose of the Study:

To evaluate the pharmacokinetic profile of lopinavir and ritonavir in a novel long-acting subcutaneous injectable formulation (TLC-ART 101).
To determine if ritonavir is essential for achieving therapeutic lopinavir concentrations in this specific dosage form.

Main Methods:

Pharmacokinetic analysis of plasma samples from subjects receiving TLC-ART 101.
Quantification of lopinavir and ritonavir concentrations over an extended period post-administration.

Main Results:

Lopinavir demonstrated prolonged plasma persistence, with detectable levels lasting up to 57 days.
Ritonavir exhibited a significantly shorter duration of detectability, ranging from 3 to 7 days.

Conclusions:

The extended half-life of lopinavir in the long-acting injectable formulation suggests that ritonavir may be dispensable.
Omitting ritonavir could lead to a reduced incidence of side effects and drug-drug interactions associated with this pharmacokinetic enhancer.