# Preclinical screening and validation for PXR-mediated herb-drug interactions associated with anti-HIV therapy

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $230,094

## Abstract

ABSTRACT
The objective of this proposal is to profile the impact of pregnane X receptor (PXR)-mediated
herb-drug interactions on the metabolism, pharmacokinetics, and toxicity of anti-HIV drugs. Herb-
drug interactions are of great concern to clinicians and pharmacists in the HIV/AIDS community
since anti-HIV drugs are frequently co-administered with herbal supplements. PXR is a ligand-
dependent transcription factor, and activation of PXR upregulates the expression of genes
encoding drug metabolizing enzymes and transporters. We recently examined 34 herbs that are
frequently used in the HIV/AIDS community, and found 9 of them to be PXR-activating herbs.
The current work will elucidate the active compounds from the complex mixtures of herbs that
activate PXR. Our recent work also determined ritonavir (RTV), an anti-HIV drug, to be a victim of
PXR-mediated drug-drug interactions. We will use RTV as an example to define the magnitude
and mechanism(s) of herb-mediated PXR activation on the metabolism, pharmacokinetics, and
toxicity of anti-HIV drugs. We will utilize genetically engineered cellular and mouse models of
PXR in the proposed experiments. The findings from this work can be used to predict and
prevent herb-drug interactions associated with anti-HIV drugs and many other drugs that are
victims of PXR-mediated drug-drug interactions.

## Key facts

- **NIH application ID:** 10232154
- **Project number:** 5R21AT011088-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Xiaochao Ma
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $230,094
- **Award type:** 5
- **Project period:** 2020-08-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10232154

## Citation

> US National Institutes of Health, RePORTER application 10232154, Preclinical screening and validation for PXR-mediated herb-drug interactions associated with anti-HIV therapy (5R21AT011088-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10232154. Licensed CC0.

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