When two or more drugs are administered concurrently, the possibility of drug interactions exists. The clinical significance of a drug metabolic interaction can have serious implications if the difference between the toxic and effective concentration is minimal and therefore it is crucial to carefully evaluate potential drug interactions of a new drug candidate during drug discovery research. An important aspect of pharmacokinetics studies during drug discovery research is ADME profiling of which drug metabolism forms an integral part. The majority of small-molecule drug metabolism is carried out in the liver by redox enzymes known as cytochrome P450 or CYP enzymes. Each CYP has the ability to metabolize multiple substrates which is responsible for the large number of drug-drug interactions associated with CYP inhibition. CYP inhibition occurs either as reversible inhibition, quasi-irreversible inhibition or irreversible inhibition.
Due to the drug-drug interactions as a result of the broad spectrum of substrates of each isoform of CYP, inhibition studies are important to perform during drug discovery research in order to develop a new drug candidate that is not a potent CYP inhibitor or inducer and the metabolism of which is not readily inhibited by other drugs. High throughput screening of potential drug candidates using high efficiency and high quality ADME profiling is available at NoAb BioDiscoveries, a research facility that helps to shape and optimize drug discovery research by focusing on lead selection and optimization. By developing innovative tools and technologies, NoAb BioDiscoveries is a cutting edge provider of in vitro ADME assays, in vivo pharmacokinetics studies, bioanalysis and gene expression assays that accelerate the drug discovery process and facilitate success in producing optimal and viable clinical candidates. In vitro ADME profiling includes assays for cell permeability, plasma protein binding, CYP inhibition, metabolic stability in hepatocytes, metabolic stability in liver subcellular fractions, plasma stability and cytotoxicity. Details on each of these assays are available at www.noabbiodiscoveries.com.
The CYP inhibition assay at NoAb BioDiscoveries is available for nine of the enzymes that include CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 and is a fluorescent based assay. The assay is ideal for rapid throughput identification of the metabolizing enzyme that interacts with a drug candidate and for the accurate and reliable prediction of the potential for a new drug to interact with co-administered drugs. Using microsomes expressing an individual CYP subtype that have been prepared from insect cells, the CYP inhibition assay monitors formation of a fluorescent metabolite following incubation of the microsomes with a specific CYP substrate. The rapid throughput CYP inhibition assay does not however, differentiate between a substrate and an inhibitor and therefore further studies are needed to characterize these compounds. An outline of the protocol used in the CYP inhibition assay and typical results are available at www.noabbiodiscoveries.com.
Although it is easy to determine in vitro drug interactions using accurate and reliable assays such as the CYP inhibition assay at NoAb BioDiscoveries, drug discovery research still requires the proper interpretation and extrapolation of in vitro interaction data to in vivo situations. NoAb BioDiscoveries additionally offers such in vivo discovery services that involve pharmacokinetics studies in rats and mice to ensure that you achieve all-round success in your drug development research. At NoAb BioDiscoveries you can be assured of accelerated drug discovery that is timely, efficient and of high quality that reduces your cost and maximizes your profit!
