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A Novel Drug-Drug and Drug-Herb Interactions Prediction Platform
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Adverse drug reactions (ADR) as a result of drug-drug, drug-herb and drug-food interactions are a growing concern in the health care setting. The cytochrome P450enzymes play a key role in the metabolism of a wide variety of compounds. Inhibition of cytochrome P450 enzymatic activities due to the presence of an inhibitor or an induction of the cytochrome by an inducer are the most common mechanisms underlying drug interactions. Predicting the ability of a drug or herbal medicine to modulate CYP expression at an early stage of drug discovery will reduce the risk of failure in the market and to ensure product safety. A drug-drug and drug-herb interaction platform service to assess the safety of drugs and standardized herbal preparations was developed. It is a triple service platform consisting of a novel multiplex qRT-PCR assay to detect the mRNA expression of CYP1A2, CYP2D6, CYP3A4, a novel in vitro CYP3A4 protein expression assay utilizing a recombinant HepG2 cell line expressing GFP protein regulated by the CYP3A4 promoter, an optimized in silico screening protocol and CYP3A4 substrate-specific inhibition assays, to assess the inhibition activities of chemical entities or standardized herbal products on the CYP3A4 enzymatic activity. Utilizing these strategies, the effects of a compound/herbal extract on the cytochrome mRNA, protein expression and enzymatic activities on liver cells can be carried out in a time saving, cost effective and high throughput manner. The safety assessments and subsequent in vitro prediction of possible risks of interactions between drugs and herbal compounds can be objectively determined.

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Organization Name
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Advanced Medical & Dental Institute, Main Campus, Universiti Sains Malaysia
13200 Kepala Batas
Pulau Pinang
Malaysia

Full Name [1]
Tan Mei Lan
Email [1]
tanml@usm.my