Drug-Drug Interaction
Creative Bioarray provides high quality drug-drug interaction services to meet FDA and EMA guidance, including identification of drug metabolizing enzymes, CYP and UGT inhibition assays, and inhibition studies towards less common metabolizing enzymes, such as MAO, FMO, NAT, AOX, and CES.
Metabolism-mediated drug-drug interactions (DDI) refer to the interference of simultaneously administered drugs with each other's ADME (absorption, distribution, metabolism, and elimination) process by inducing or inhibiting the activities of drug metabolizing enzymes and/or drug transporters. Concomitant medications may result in an abrupt alteration in metabolism or transport that can lead to an unwanted augmentation or decrease in the blood level of a drug administered to a patient, changing the known safety and efficacy of a drug and leading to severe side effects. Thus evaluation of new drug candidates for DDI is recommended by the US Food and Drug Administration (FDA)1.
Figure 1. CYP3A induction2
The study of DDI for a new drug usually starts with in vitro studies to determine whether a drug is a substrate, inhibitor, or inducer of metabolizing enzymes. The assays can be carried out either at sub-cellular level or at cellular level.
Creative Bioarray provides a range of high quality in vitro DDI assessment services, including:
Enzyme Inhibition Assays
- CYP- and UGT-reaction phenotyping
- Cytochrome P450 induction and inhibition assays
- UGT inhibition (and other non-CYP enzymes)
- UGT induction
- Drug transporters
- Detailed Ki service and Kinact/Ki service
- CYP450 time dependent inhibition (TDI) assay
Transporter Inhibition and Substrate Assays
Apart from enzyme inhibition, transporter inhibition and substrate identification have gradually become the spotlight of drug-drug interaction (DDI) research. Drug transporters play an increasingly important role in drug development because of transporter mediated DDI and its correlation with potential pharmacological and toxicological outcomes.
- Transporter inhibition:
- Permeability assays:
- Caco-2 permeability:
- MDR1-MDCK permeability:
- Efflux transporter substrate determination:
Inhibition of efflux transporters has been demonstrated to be responsible for interactions between drugs. Our services include P-gp, BCRP, BSEP and MRP inhibition assays.
Our Caco-2 permeability assays can be combined with the known P-gp or BCRP inhibitor to investigate whether active efflux is mediated via these transporters.
This strategy can be used to determine whether your compound is the substrate of P-gp.
Investigate the possibility of the test compound to be a substrate of efflux transporter. The relevant assays we can offer you, including the determining the substrate of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), the solute carrier (SLP), multidrug resistance-associated protein (MRP), and bile salt export pump (BSEP).
Creative Bioarray is dedicated to providing fast and integrated services of the highest quality to accelerate drug discovery process. With years of experience and deep knowledge in drug development, our scientific team is ready to serve you with flexible assays and tests. If you have any special needs or questions regarding our services, please feel free to contact us to get support from our experienced experts. We look forward to working with you in the future.
References
- US Food and Drug Administration. "Drug Interaction Studies–Study Design, Data Analysis, Implications for Dosing, and Labeling Recommendations." Center for Drug Evaluation and Research, FDA, Bethesda, MD (2012).
- Willson, Timothy M., and Steven A. Kliewer. "PXR, CAR and drug metabolism." Nature reviews Drug discovery 1.4 (2002): 259-266.
