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Herb-Drug Interactions

Pharmacokinetic Interactions

several potential interactions between TCM herbs and formulations and Western therapeutics have been reported, and these are typically pharmacokinetic-based, where the phytochemicals in herbs can be substrates, inhibitors, or inducers of various CYp enzymes, thereby changing the pharmacokinetic profiles of the concurrently administered drug or metabolites. Chan2 described the continual need for and the difficulties in obtaining accurate information on interactions in the practice of integrative medicine. some of the issues include the evaluation of in vitro data, quality of chemicals used in the various assays, and comparison to human case studies. approaches to meet those needs include the development of the Herbal ingredient Metabolism database (him) by Kang et al.4S the database collects almost all the available in vivo metabolism information for herbal active ingredients, as well as their corresponding bioactivity, organs and/or tissues distribution, toxicity, ADME data, and the clinical research profile when possible. Currently, HiM49 contains 361 ingredients and 1104 corresponding in vivo metabolites from 673 reputable herbs. TooIs to investigate structural similarity, substructure search and Lipinski’s rule of five are also provided. Various links are also available to PubChem, PubMed, TCM-ID and HIT.

Wu et al.50 reviewed the most common herbs used in TCM formulations and highlighted the current understanding of phytochemicals acting as substrates, inhibitors, or inducers of human CYP enzymes. Cho and Yoon51

Table 12.2 Analysis of selected therapeutic classes and their respective predicted targets.0

Cell survival

Cell survival and immune response

Metabolism, apoptosis and cell cycle

EGFR

p53

JNK

p38

ERK1/2

IKK beta

OT-kappa B

pkr

GsK3 beta

pi3K

akt

Heat clearance

1

1

Tonifying weakness

7

2

3

3

3

Promoting diuresis and

4

1

3

1

2

1

2

1

2

1

1

penetrating dampness

“In this table, the predicted targets were grouped based on the main downstream effects. It shows clearly that herbs in the therapeutic class of “heat clearance” only interact with targets that are responsible for cell survival, while those in the class of “promoting diuresis and penetrating dampness” interact with those responsible for immune response and metabolism, in addition to cell survival.

reviewed the modulation of CYP enzymes and P-glycoprotein by 10 popular medicinal and/or dietary herbs and their phytochemicals in relationship pharmacokinetic interactions. Evidence included in vitro, in vivo, and human-based assays. Tsai et al.52 reviewed the interactions between antico- agulant/antiplatelet therapeutics and TCM. they discuss 306 documented interactions; 155 were attributable to pharmacodynamic factors; almost all were rated as moderate to severe. In another study, Tsai et al.53 compiled an extensive search and documented herbs and dietary supplement interactions with the concomitant use of drugs. their data show that formulations and products containing st John’s wort, magnesium, calcium, iron, and ginko had the highest number of documented interactions, and flaxseed, Echinacea, and yohimbe had the highest number of documented interactions. Western therapeutics affecting the central nervous and cardiovascular systems had the highest documented interactions with herbal medicines. Wan- wimolruk et al.54,5S in two publications, review several herb drug interactions, observing that most information derives from animal and in vitro studies. The authors highlight the importance of confirming current evidence with clinical studies.

Detailed information on herbal medicines can be found at Medline Plus.56 Summaries of information include answers to the questions What is it? How effective is it? How does it work? Are there safety concerns? Are there interactions with medications? Are there interactions with herbs and supplements? Are there interactions with foods? What dosage is used? Plus other names, methodology, and references.

MediHerb provides a chart of potential herb-drug interactions for commonly used herbs.57

Pharmacogenomic-Related Interactions

Although multiple reports have been published on the interactions of herbs and drugs, and most of the interactions involve metabolizing enzymes and transporters, very few reports exist on pharmacogenomic-related interactions. For each of the different enzymes and transporters, there are known polymorphisms that have been shown to affect the intended therapeutic outcomes with Western therapeutics and several of these appear in the approved labeling of these drugs. Liu et al.41 highlighted these polymorphisms and drew correlations with various herbal medications based on the known information based on substrate, inducer, or inhibitor molecular interactions. This research, while very important, still remains at an early stage.

 
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