Drug-Drug Interaction Analysis Service

Drug-drug interaction (DDI) refers to the phenomenon that concurrent drugs affect each other's drug activity by inducing or inhibiting drug metabolic enzymes or transporters during the process of absorption, distribution, metabolism and excretion (ADME). This process may cause abnormal changes in drug metabolism, resulting in abnormal increases or decreases in blood drug concentration, that may lead to severe side effects or diminished efficacy. Therefore, DDI is a test item recommended by the FDA for new drug development.

Creative Biolabs provides in vitro drug toxicological evaluation services, including DDI studies. With the world's leading technology and many years of experience in drug development and toxicity detection, Creative Biolabs can help you to achieve the following exploration of DDI: (1) Confirmation/discovery of interactions predicted by early studies (preclinical in vitro); (2) Verify that dosing adjustments or other changes in prescription information for potential interactions are sufficient to prevent DDI from occurring; (3)To avoid the occurrence of low dose less than effective window and high dose more than toxic window in the course of clinical drug combination after the drug is on the market. With its global talent and technical advantages, Creative Biolabs has formed a complete one-stop service platform in the field of drug toxicity detection about DDI, providing a strong impetus for the sustainable development of drug research and development.

We provide but are not limited to:

Cytochrome P450 (CYP450) enzyme induction/inhibition assay. CYP450 which is an important drug metabolizing enzyme in the liver plays a crucial role in the biological transformation of exogenous and endogenous substances. The change of CYP450 enzyme activity/content directly affects the effective amount and action time of metabolized drugs in vivo, which is closely related to the efficacy and drug safety.

Phenobarbital is the inducer of CYP450 and actinomycin D is the inhibitor of CYP450. The effects of phenobarbital and actinomycin D on liver CYP450 are compared with tested sample, which can be used as one of the screening methods for liver drug enzyme inducer and inhibitor. CYP450 is a heme protein. After its reduced form combines with CO, the absorption peak appears at the wavelength of 450nm. The absorbance value of the solution can be determined to reflect the content of CYP450 enzyme in the solution.

UDP-glucuronosyltransferase (UGT) inhibition assay. UGT family is the second largest drug metabolizing enzyme in human body after CYP450 family. UGT - mediated glucuronic acid conjugation not only significantly affect the oral bioavailability of drugs and drug pharmacokinetic process of the body, but also relate to some clinical drug - drug interactions, drug - herbs interactions and drug - food interactions. In addition, it is also closely related to the occurrence of a variety of diseases such as high bilirubin hematic disease, cancer and autoimmune hepatitis.

In vitro incubation of liver microsomes. Uridine diphosphate glucuronic acid (UDPGA) is catalyzed by uronyltransferase in the prepared liver microsomes. The metabolic reaction is simulated in vitro under physiological environmental conditions. After a certain period of time, HPLC, HPLC - MC and HPLC - MC /MC are used to determine the residual contents of the prototype drugs in warm incubation liquid.
The stability of II phase metabolic reactions kit. Aiming at the need of drug metabolism study, the kit can be directly used in the stability study of II phase metabolic reactions, eliminating the tedious process of preparation of liver microparticles and reagents, which greatly shortens the experimental period. The experimental results are accurate, reliable and reproducible.

Drug transporter assay. DDI associated with transporters plays an important role in the development of new drugs. Transporters include p-glycoprotein (P-gp), organic anion transporter (OAT), organic anion transporter peptide (OATP), organic cation transporter (OCT), multi-drug resistance related protein (MRP) and breast cancer drug resistance protein (BCRP). Among the various transporters, we can provide P-gp as the most fully studied transporter to evaluate drug interactions in the development of new drugs.

To test whether the test drug is a P-gp inhibitor or inducer, digoxin or other known P-gp substrates can be selected.
To test whether the test drug is a P-gp substrate, P-gp inhibitors (such as ritonavir, cyclosporine and verapamil) or inducers (such as rifampicin) can be selected.
When the test drug is both P-gp and CYP3A substrate, the strong inhibitor (such as ritonavir) can be selected.

The popular services：

HTS and HCS platform. High-throughput screening (HTS) and high-content screening (HCS) platform is a ideal platform of cellular and subcellular level function research. It is a combination of high speed multi-channel imaging detection technology and powerful analysis software for multiple parameter analysis, which can quickly capture cellular, subcellular and tissue image, realizing the fast high quality detection of large sample. It is the ideal platform for high-throughput screening.

Creative Biolabs has many years of practical experience in HTS/ HCS imaging and analysis, carrying out a variety of in vitro drug toxicological screening services efficiently and quickly.

Advantages of drug-drug interaction assay services:

Honest, practical and efficient.
International leading talent team.
High performance-price ratio.
Scientific and technological innovation.

References

Rekić D, et al. Clinical drug-drug interaction evaluations to inform drug use and enable drug access. J Pharm Sci. 2017, 106(9):2214‐2218.
Min JS, et al. Prediction of drug-drug interaction potential using physiologically based pharmacokinetic modeling. Arch Pharm Res. 2017, 40(12):1356‐1379.
Shuai Z L, et al. Review of high-content screening applications in toxicology. Archives of Toxicology, 2019, 93(12): 3387-3396.

*For Research Use Only. Not for use in diagnostic procedures.

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