Fall 2018
Botanical Drug Interactions Image
Hepatic Model Helps to Predict Clinically-Relevant Botanical-Drug Interactions
By Dr Amy L. Roe and Dr Jonathan P. Jackson
Fall 2018

Use of botanical-based dietary supplements is increasing among people of all ages and in most geographies. Most of these populations have ready access to conventional medications, with significant polypharmacy observed in older adults.

The scientific literature is replete with reports of botanical extracts and/or their constituents as potent inhibitors of drugmetabolising enzymes and transporters. Unfortunately, most of these studies use simplistic in vitro screening-based systems without follow-up in more physiologically-relevant models. Additionally, the potential for botanical extracts to induce metabolic enzymes and/or transporters is rarely studied, particularly in in vitro systems.

Thus, in the rare instances when clinical studies are conducted to confirm botanical-drug interaction (BDI) potential, there is usually a poor correlation between in vitro studies and clinically-relevant changes in the pharmacokinetics of drugs under study.

New paradigms are necessary to assess BDIs. One such method uses sandwich-cultured human hepatocytes and an in vitro clearance approach that treats the complex botanical mixture as a single entity, regardless of the constituent profile. This in vitro approach captures the major hepatic drug clearance pathways and provides predictions that are easily translatable to the clinic. Thus, it identifies potentially significant and insignificant interactions.

By studying complex mixtures using this method it is possible to evaluate the overall net effect on drug clearance mechanisms and capture synergism and additive effects that occur among the constituents within these complex mixtures – effects that may not be observed with a traditional deconstructionist approach.

This case study will show how the sandwich-cultured human hepatocytes model was used to predict clinically-relevant BDIs using Schisandra spp. It also potentially demonstrates applications for the sandwich-cultured human hepatocytes model in evaluating BDIs for other herbal extracts and for identifying hepatotoxicity endpoints.

Introduction

Rising sales of botanical supplements leads to increasing concern about BDIs

In 2017, botanical-based dietary supplements surpassed $8 billion in sales, and showed the greatest growth in 15 years (1). The consistent increase in supplement sales during the past decade reflects consumers’ interest in alternative health approaches (eg Ayurvedic herbs, traditional Chinese medicine), new formulation options (enhanced absorption technologies) and culinary botanicals with general health and nutrition benefits.

The increase in dietary supplement popularity, coupled with the already heavy use of prescription drugs in the US, highlights the importance of studying BDI potential (2). Further adding to the risk of concomitant use interactions is the documented lack of dialogue between patients and healthcare professionals about dietary supplement use, despite media attention warning about potential BDIs. We believe that providing information on potential BDIs can facilitate informed decisionmaking by consumers and healthcare providers.....

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