When two or more drugs are administered concomitantly, the reactions that occur between the drugs can have an impact on the pharmacokinetic (PK) or pharmacodynamic (PD) properties, and these interactions can lead to increased or decreased drug exposure. Drug-drug interaction ( DDI ) risk assessment is an important part of drug safety assessments required by drug regulatory authorities. BOC Sciences provides high-quality DDI assay services with a complete ADME assay system, including the identification of metabolic enzymes, enzyme inhibition and enzyme induction assays, and transporter-mediated DDI interactions.

Interactions during drug absorption may alter the drug absorption and the therapeutical efficiency. Metabolism-mediated DDI means that two or more drugs administered simultaneously interfere with each other’s ADME process by inducing or inhibiting the activity of drug metabolizing enzymes and/or drug transporters. This may lead to increased or decreased pharmacological effects of the drug, or new adverse effects. Therefore, detailed assessment of the interaction potential of lead compounds is critical during drug development, starting with preclinical in vitro and in vivo studies for candidate selection and continuing through preclinical and clinical development.

• CYP Inhibition

Inhibition of cytochrome 450 (CYP) by new chemical entities is associated with the increased incidence of DDI, and the characterization data of CYP inhibition can also provide reference for the design of clinical DDI research strategies. Combined with LC/MS/MS analytical techniques, BOC Sciences uses liver microsomes or recombinant CYP enzymes to assess the potential of compounds to inhibit specific CYP enzymes for possible mechanisms of inhibition. Furthermore, BOC Sciences offers time-dependent inhibition (TDI) assays for CYP450, including IC50 shift and Kinact/KI assays.

• UGT Inhibition

Uridine glucuronyl transferases (UGTs) play key roles in the phase II metabolism of most drugs and the biotransformation of many endogenous products such as bilirubin. Therefore, it is important to detect the inhibitory effect of candidate lead compounds on UGT in the early stage of drug discovery. BOC Sciences’ UGT inhibition assay service uses recombinant UGT enzymes for screening. Our LC/MS/MS analytical technology enables precise monitoring of the formation of UGT-specific probe metabolites for regulatory assessment of UGT inhibition.

• Other Metabolising Enzymes Inhibition

Some drugs are not metabolized by CYP or UGT enzymes, but can be metabolized by other enzymes. These enzymes can also be inhibited or induced by drugs, leading to drug-drug interactions. BOC Sciences’ DDI service also includes assays for these uncommon drug metabolizing enzymes, including flavin-containing N-acetyltransferase (NAT), monooxygenase (FMO), monoamine oxidase (MAO), and carboxylesterase (CE) , aldehyde oxidase (AOX), xanthine oxidase (XO), sulfotransferase (SULT).

• CYP Induction

The CYP enzyme family plays an important role in drug metabolism, and the induction of CYP is closely related to the incidence of clinical DDI. For example, the induction of CYP by new chemical entities may lead to an increase in the number and activity of CYP metabolized by related drugs, which may lead to enhanced metabolism of combination drugs. BOC Sciences can tailor cost-effective CYP induction screening strategies to specific client requirements. Our standardized CYP induction services meet professional standardsand EMA guidelines and provide reliable, high-quality, and reproducible test data.

• UGT Induction

In addition to CYP, candidate lead drugs also induce UGT enzymes and affect the absorption, distribution and elimination of drug molecules in vivo. Currently, 15 functionally active human UGTs have been characterized and divided into two subfamilies (UGT1 and UGT2) based on amino acid sequence similarity. BOC Sciences is capable of offering hepatocyte induction assays for the UGT1A1, UGT1A9 and UGT2B7 subtypes. Our screening experiments can be used for lead compound selection and early determination of DDI potential. Testing programs that comply with industry-related regulatory submissions can meet customers’ customized research needs.

• Transporter Interactions

Drug induction and/or inhibition of transporters in tissue barriers can affect the uptake and efflux of drugs and drug metabolites, resulting in drug-drug interactions. DDI may affect the absorption, distribution and elimination of drugs in the body, resulting in serious drug side effects. Based on industry regulatory guidelines, BOC Sciences offers assay characterization services for uptake transporters, efflux transporters, and vesicular membrane transporters. The in vitro data we provide, as well as estimates of in vivo local plasma and tissue concentrations, can be used to assess whether candidate compounds require further clinical studies.