Metabolism plays a major role in both the efficacy and safety of drugs. Drug Metabolism Studies by screening compounds early in the drug discovery process is essential for selecting candidates with desirable drug metabolism and pharmacokinetic – DMPK profiles.
GVK BIO Drug Metabolism Studies has a leading portfolio of in vitro services designed to help you understand the metabolic profile of your compound. We offer extensive phase I and phase II enzyme assays, including cytochrome P450 (CYP) inhibition and CYP induction assays in all the major isoforms (3A4, 2D6, 2B6, 1A2, 2C8, 2C9, 2C19) and UGT phenotyping and inhibition experiments. Our metabolic stability assays measure the intrinsic clearance of your compound and we provide detailed metabolic profiling for metabolite identification as well as reactive metabolite screening using state-of-the-art Mass Spectrometry instrumentation.
A drug that is rapidly metabolised may require multiple daily dosing or continuous infusion to maintain a concentration in the bloodstream or target organ that is sufficient to elicit a therapeutic effect. However, a slowly metabolised drug may remain in the body for long periods, causing toxic build-up.
For compounds which have a particularly low clearance, accurate extrapolation of the in vitro intrinsic clearance to the in vivo situation can be challenging using the standard methods. GVK BIO has validated a low clearance hepatocyte stability method to specifically address this issue using plated hepatocytes over longer incubation times. We can also assess hepatic uptake using the media loss assay which takes into account the active uptake into hepatoocytes by drug transporters.
Our metabolism assays are available in various test systems, including recombinant CYP’s, liver microsomes and hepatocytes from multiple species, and can be ordered individually, combined or as a selection of key services provided in our drug candidate assessment packages to provide cost savings.
We also have a variety of other drug metabolism services available including:
- Compound testing for blood and plasma stability
- Glucuronide and glutathione conjugation
- Nuclear receptor activation of PXR, AhR, and CAR
- Drug transporter services in Caco-2, MDCK, membrane vesicles, and transfected cells lines
- Transporter screening for P-gp, BCRP, MRP2, BSEP, OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2, MATE1, MATE2-K and more
- A range of testing services to help investigate toxicities related to poor ADME and PK properties
- Drug-Drug Interactions
- Lead optimization services