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Emerging In Vitro Tools to Evaluate Cytochrome P450 and Transporter-Mediated Drug-Drug Interactions

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Drug-drug interactions DDI comprise a significant cause of morbidity and mortality worldwide as they may lead to adverse clinical events, result in decrease/inactivation of the therapeutic effect of a drug, may enhance drug toxicity and indirectly compromise treatment outcomes and adherence. Drug transporters and drug metabolism enzymes govern drug absorption, distribution, metabolism, and elimination (ADME). Inhibition or induction of transporter and drug metabolism enzymes can alter the ADME of a co-administered drug, which may lead to drug-induced toxicity or lack of efficacy. This review assesses our current understanding of the in vitro methods of evaluating CYPs and transporter- mediated DDI. The DDI prediction models based on in vitro assays are also discussed in this review. The applications, advantages and limitations of each method are also addressed in this review.





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Keywords: ADME; ATPase assay; BCRP; CYP; CYP1A2; CYP2B6; CYP2C19; CYP2C8; CYP2C9; CYP2D6; CYP3A4; Caco-2; Calcein-AM; Cyclosporine A; DDI; DDI prediction; Drug-drug interaction; HMG-CoA; HPLC; HepaRG cells; Human Liver Microsomes; MBI; MDCK; MRP2; MXR; Mechanism-based CYP inhibition; Modified Shift Assay; Multiple Clearance Path-ways; NADPH; NCE; NTCP; OAT; OATP; OATPs; OCT; P-gp; PXR; Phase 0 metabolism proteins; Polypharmacy; Simple Reversible DDI Prediction Model; TDI Prediction Model; UGT1A1; cytochromes; cytochromes P450; drug metabolism enzyme; drug transporters; fexofenadine; high pressure liquid chromatography; in vitro tools; mass spectrometry; mitoxantrone re-sistance protein; multidrug resistance protein 2; new chemical entity; organic anion transporting polypeptides; pregnance X receptor; pseudo 1st order reac-tion; rifampin; time-dependent inhibi-tion

Document Type: Research Article

Publication date: 01 September 2010

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  • Due to the plethora of new approaches being used in modern drug discovery by the pharmaceutical industry, Current Drug Discovery Technologies has been established to provide comprehensive overviews of all the major modern techniques and technologies used in drug design and discovery. The journal is the forum for publishing both original research papers and reviews describing novel approaches and cutting edge technologies used in all stages of drug discovery. The journal addresses the multidimensional challenges of drug discovery science including integration issues of the drug discovery process.

    Current Drug Discovery Technologies is an essential journal for all scientists and research managers involved in drug discovery who wish to keep abreast of all the modern techniques and technologies used in drug discovery.
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