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Updated: Jul 13, 2026

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

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Interaction between lopinavir/ritonavir and warfarin.

Christine A Hughes¹, Andrea Freitas, Lilly J Miedzinski

¹Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alta. chughes@pharmacy.ualberta.ca

CMAJ : Canadian Medical Association Journal = Journal De L'Association Medicale Canadienne

|August 19, 2007

Summary

Protease inhibitors used in HIV therapy can affect blood thinner warfarin levels. Co-formulated lopinavir/ritonavir led to a significant decrease in a patient

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Area of Science:

Pharmacology
Drug Metabolism
Drug Interactions

Background:

Protease inhibitors (PIs) are critical in HIV treatment.
Many PIs inhibit the cytochrome P450 3A4 (CYP3A4) enzyme.
Some PIs, like lopinavir/ritonavir, can also induce other metabolic pathways.

Observation:

A patient on warfarin experienced a reduced international normalized ratio (INR).
This reduction occurred after starting antiretroviral therapy (ART) with lopinavir/ritonavir.
Warfarin dosage adjustments were necessary.

Findings:

Lopinavir/ritonavir likely induced warfarin metabolism, leading to lower INR.
This suggests a complex drug interaction beyond simple CYP3A4 inhibition.
Other PIs have also shown interactions with warfarin.

Implications:

Clinicians must monitor INR closely in patients taking warfarin and PIs.
Understanding PI-induced metabolic changes is crucial for managing anticoagulation.
Further research into PI-drug interactions is warranted to ensure patient safety.