ADME / Tox >> Drug-Drug Interactions >> Metabolism / Stability

Avoid being misled by insoluble compounds

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Undesirable ADME properties are major factors causing failures during drug development. To prevent these costly failures from occurring, in vitro screening of potential drug candidates in the early drug discovery phase has been employed as a cost-effective approach to identify compounds with unfavorable ADME characteristics. Eurofins provides a wide variety of metabolism screening assays using assay matrices, including: recombinant cytochrome P450 enzymes (CYPs), recombinant uridine diphosphate-glucuronosyl transferases (UGTs), liver microsomes and hepatocytes from human and animal species.

After entering the body, a drug will be metabolized to one or several more water-soluble metabolites, which can be more readily excreted than the corresponding parent drug. The enzymes that catalyze chemical conversion during the metabolism process are categorized as phase I (mainly CYPs) and phase II (such as glutathione-S-transferases and UGTs) drug-metabolizing enzymes. These enzymes are present at high levels in organs of elimination, such as the liver, intestine, and kidney. Intrinsic clearance assays using liver microsomes or hepatocytes will allow you to estimate the extent of metabolic clearance and first-pass effect for your compounds. Further studies of CYP- and UGT-reaction phenotyping will allow you to understand whether your compound is subject to drug-drug interactions or polymorphic effect.

By partnering with Eurofins, you'll be able to better understand your drug candidate's metabolism and stability and obtain a more comprehensive assessment of that compound's drug profile.

In vitro metabolism screening assays allow identification of compounds that have these favorable characteristics:

  • Stability - small first-pass effect to maintain an effective concentration in blood for a reasonable period of time
  • Metabolized by multiple CYP enzymes and not largely dependent on CYPs that are polymorphically-expressed, such as CYP2C9, CYP2C19, and CYP2D6
  • Lead to no pharmacologically-active (unless starting as a pro-drug) or chemically-reactive metabolites