XBL * A subsidiary of Lab Testing Division, WuXi AppTec Inc. WuXi AppTec XBL * A subsidiary of Lab Testing Division, WuXi AppTec Inc. WuXi AppTec
Sunday, September 24, 2017

In vitro Drug-Drug Interaction (DDI) Services

"Drug interactions can result when one drug alters the pharmacokinetics of another drug or its metabolites" (FDA Guidance on Drug Interaction Studies, Feb. 2012). The FDA guidance recommends that "The study of drug-drug interaction for a new drug generally begins with in vitro studies to determine whether a drug is a substrate, inhibitor, or inducer of metabolizing enzymes". FDA and EMA (Guideline on the Investigation of Drug Interactions, June 2012) guidance's also outline a strategy for in vitro testing of transporter-mediated drug-drug interactions. WuXi/XBL provides a complete set of in vitro DDI studies as part of its comprehensive ADME/DMPK services.

In vitro DDI services include:

CYP Enzymes:

  • CYP Inhibition (7-9 CYPs) - direct (DI) and time-dependent (TDI). Determine IC50, Ki, KI, Kinact as needed.
  • CYP Induction (mRNA and activity assays -1A2, 3A4, 2B6)
  • CYP Substrate Phenotyping (7-9 CYPs)
    • Substrate depletion or,
    • Formation of key metabolites in HLM (Km, Vmax), with/without selective chemical inhibitors
    • rhCYPS
  • UGT / FMO Substrate Phenotyping

Transporters – Substrate and Inhibition assays

  • Membrane vesicles – Efflux transporters (BCRP*, MDR1[P-gp]*, BSEP, MRP1, MRP2, MRP3, MRP4)
  • Cell-based assays
    • Uptake transporters – OAT1*, OATP1B1*, OATP1B3*, OCT1,OAT3*, OCT2*, PEPT1, 2, MATE1, 2 in CHO cells, OAT3* in 2K, NTCP, ASBT and others
    • Efflux transporters – BCRP* and MDR1[P-gp]* in transfected MDCKII and Caco-2 cells
    • Double transfected – BCRP±OATP2B1 in double transfected MDCKII cells
  • *FDA (Feb, 2012) and EMA (June 2012) recommended
  • EMA (June, 2012) recommended

Substrate/metabolite assay by LC-MS or radiolabel profiling/counting

Integration with metabolism pathway determination and metabolite structure elucidation/confirmation including 500 MHz NMR analysis

WuXi/XBL offers its DDI studies as either non-GLP or in compliance with GLP regulations

WuXi/XBL provides CYP services at both its locations (NJ; China) and provides transporter services in NJ in collaboration with Solvo® Biotechnology and thus offers fully integrated DDI services based on many years of experience.