# Pharmacology Core

> **NIH NIH U54** · WASHINGTON STATE UNIVERSITY · 2020 · $741,992

## Abstract

PROJECT SUMMARY OF THE PHARMACOLOGY CORE
Sales of botanical and other natural products (NPs) continue to rise exponentially, increasing concerns for
adverse interactions between NPs and concomitant prescription medications. During the first four-plus years of
our Center of Excellence for Natural Product Drug Interaction Research (NaPDI Center), the Pharmacology
Core established a framework for the selection, prioritization, and evaluation of high impact NPs as precipitants
of potential clinically significant pharmacokinetic NP-drug interactions (NPDIs) that could lead to suboptimal
therapeutic outcomes. We adopted a rigorous, systematic ‘predict, learn, and confirm’ approach involving robust
human-relevant in vitro systems, pharmacokinetic modeling and simulation, and clinical evaluation to assess the
clinical relevance of NPDIs. The Pharmacology Core component of this renewal application proposes three
SPECIFIC AIMS that refine and extend the ‘best practices’ developed during the initial funding period. AIM 1: the
Pharmacology Core, in collaboration with the Analytical Core, Informatics Core, Administrative Core, and
Steering Committee, will select and prioritize three to five widely used NPs as precipitants of potential clinically
significant NPDIs using our established method termed the fulcrum model. Based on our experience to date, we
have expanded this innovative model to include a fast track option that accommodates emerging NPs with
heightened NPDI risk to remain responsive to public health needs. The following high priority NPs are proposed:
kratom, hemp products, cinnamon, black pepper supplement, and the combination product Echinacea
purpurea/goldenseal. AIM 2: the Pharmacology Core will evaluate the NPDI liability of these NPs using
established human in vitro systems for both drug metabolizing enzyme and transporter activity and in vitro to in
vivo extrapolation approaches recommended by the Food and Drug Administration. AIM 3: the Pharmacology
Core will evaluate the clinical NPDI risk in healthy volunteers that will include a more vulnerable, elderly
population. The rationale for targeting the latter group is that specific NPs are increasingly marketed to the aging
population, often claiming fewer side effects than prescription medications. The Pharmacology Core’s clinical
research capabilities are a cornerstone of the NaPDI Center, having completed five clinical studies during the
initial funding period. Throughout the proposed project, NPs that emerge from companion R21 grants will be
applied to our expanded fulcrum model and potentially advanced to our NP list. We will continually integrate new
clinical research methods, such as evaluating the effects of the gut microbiota and incorporating transporter
probe cocktails and biomarkers of drug metabolizing enzymes and transporters. The Pharmacology Core, in
synergy with the other Cores of the NaPDI Center, has efficiently and definitively established a new standard for
NPDI research....

## Key facts

- **NIH application ID:** 10062145
- **Project number:** 2U54AT008909-06
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** MARY F PAINE
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $741,992
- **Award type:** 2
- **Project period:** 2015-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10062145

## Citation

> US National Institutes of Health, RePORTER application 10062145, Pharmacology Core (2U54AT008909-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10062145. Licensed CC0.

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