Drug-Drug Interactions (DDIs) Services
Drug-drug Interactions (DDIs) happen when one drug changes the metabolism of another drug. DDIs risk assessment is an important component of the drug safety review needed by regulatory agencies. According to the FDA and EMA guidelines on medication interaction studies, experimental drugs should be examined for their ability to inhibit or induce metabolic enzymes and drug transporters associated with clinically meaningful drug interactions. To assist our partners in reducing these risks for new pharmaceuticals, Creative Biolabs provides a comprehensive suite of DDIs services.
Available Assays
CYP Inhibition
Inhibition of cytochrome P450 (CYP) enzymes by novel chemical entities may reduce the metabolism of concomitant drugs. We provide assays that target specific enzymes as well as cocktail methods for determining inhibition of numerous enzymes in the same incubation. Screening assays were run using up to eight cytochrome P450 enzymes (1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4) and nine probe reactions. Direct inhibition assays provide IC50 values and estimated Ki values for each CYP enzyme. The TDI assay provides direct and offset IC50 values for each CYP enzyme.
- CYP inhibition is one of the most relevant mechanisms of DDIs.
- Direct inhibition with N-in-one or independent CYP tests.
- Time-dependent inhibition (TDI); caused by reactive/inhibitory metabolites.
- LC/MS/MS analysis.
UGT Inhibition
UGT inhibition tests using recombinases with particular substrates and multiple inhibitor concentrations can be carried out on isoforms UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7, and UGT2B15, providing IC50 values for particular UGTs.
- Using recombinant UGT enzymes for screening.
- Using LC/MS/MS analysis to track the formation of UGT-specific probe metabolites.
CYP Induction
- Using mRNA and/or CYP activity level endpoints.
- Screening using PXR nuclear receptor activation.
UGT Induction
- Using mRNA and/or UGT activity level endpoints.
Inhibition of Other Metabolic Enzymes
Some compounds cannot be significantly metabolized by CYP or UGT, but they can be metabolized by other enzymes such as sulfotransferase (SULT), flavin monooxygenase (FMO), monoamine oxidase (MAO), N-acetyltransferase (NAT), aldehyde oxidase (AOX), or carboxylesterase (CE). As part of our DDIs services, we provide inhibition studies for these less common drug metabolizing enzymes. These experiments can provide IC50 values for a specific enzyme by employing recombinant enzymes, specific substrates, and different inhibitor doses.
Transporter protein assay
- ABC Transporter Phenotyping
- ABC Transporter Inhibition
- SLC Transporter Phenotyping
- SLC Transporter Inhibition
DDIs Expertise
- In vitro assays using radiolabeled and/or unlabeled test compounds.
- Senior in vitro scientists offer experienced data review and analysis.
- Tailored in vitro programs to meet your specific needs.
Would you like to learn more about how we can help you? Please contact us so that we may discuss this.
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