Multiple P450 substrates in a single run: rapid and comprehensive in vitro interaction assay.

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Turpeinen M, Uusitalo J, Jalonen J, Pelkonen O

Multiple P450 substrates in a single run: rapid and comprehensive in vitro interaction assay.

Eur J Pharm Sci. 2005 Jan;24(1):123-32.

PubMed ID

15626586 [ View in PubMed

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Abstract

The dramatically increased number of new chemical entities (NCE) used in drug discovery has raised a demand for efficient and rapid drug metabolism screening techniques. The aim of this study was to develop a global in vitro metabolic interaction screening test utilising the N-in-1 approach. A cocktail consisting of 10 CYP-selective probes with known kinetic, metabolic and interaction properties in vivo was incubated in a pool of human liver microsomes, and metabolites of melatonin (CYP1A2), coumarin (CYP2A6), bupropion (CYP2B6), amodiaquine (CYP2C8), tolbutamide (CYP2C9), omeprazole (CYP2C19 and CYP3A4), dextromethorphan (CYP2D6), chlorzoxazone (CYP2E1), midazolam (CYP3A4) and testosterone (CYP3A4) were analysed simultaneously using LC/TOF-MS. Performance of the method was assessed with cDNA expressed P450s and diagnostic CYP-specific inhibitors. The results were in good accordance with literature and our previous studies. The cocktail developed is suitable for fast and reliable in vitro screening of the interaction potential and characteristics of NCEs.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Melatonin	Cytochrome P450 1A2	Protein	Humans	Unknown	Substrate	Details
Omeprazole	Cytochrome P450 3A4	Protein	Humans	Unknown	Substrate Inhibitor Inducer	Details