Drug Metabolism and Safety Toxicity Testing Services
Improve your chances of clinical success with our fast-track services
Using our world-leading in vitro liver-on-chip model
Obtain human translatable insights from your lead candidates
Get results within just a few weeks
Lower cost versus animal studies
Better informed pre-clinical decisions
Drug Metabolism Testing
Study the human metabolism of lead candidates, identify metabolites and correlate with cell health – even for low clearance compounds
Safety Toxicity Testing
In–depth analysis of acute or chronic drug induced liver injury using a wide range of endpoints to determine causality and mechanism of toxicity
Research Collaborations
CN Bio is uniquely placed to build novel multi-organ systems to meet your workflow and knowledge gaps
Drug Metabolism Testing
Standard in vitro DMPK studies face many challenges including: incompatibility with new therapeutic modalities, inaccurate predictions of human in vivo clearance rates (particularly for low clearance compounds) and missing rare or human-specific metabolites.
By testing your lead candidates against our human liver-on-chip model, the risk of an unexpected late-stage surprise is reduced. Our long term and multifunctional liver culture is compatible with a wide variety of different drug modalities. It is suitable for the mono or co-culturing of human (or animal) cells and can be utilized for a variety of single and multi-organ ADME applications.
With high metabolic activity and cellular functions maintained for at least 4 weeks, our liver-on-a-chip combined with LC-MS analysis enable the generation of temporal (repeat sampling) metabolite profiles capturing phase I and II metabolism. It is also possible to differentiate and quantify a wide range of compound clearance rates, including slowly metabolised drugs.
The performance of our Liver-on-a-chip significantly out-performs the drug metabolism capabilities of equivalent cells plated in 2D, and predicted clearance rates for a range of well-known drugs tested show good agreement with in vivo clinical data (Tsamandouras et al., 2017).
Furthermore, direct correlations between metabolite formation and liver toxicity can be derived from the same sample using cell health measurements to flag any potential adverse effects whilst multi-organ studies offer the ability to more accurately determine bioavailability by linking the liver to a barrier model to evaluate drug absorption and metabolism within one interconnected system.
- Individual human donors, or pools from varying genetic backgrounds
- Full range expression of CYP enzymes (cytochrome p450s)
- High metabolic activity maintained for at least 4 weeks
- Generate temporal human metabolite profiles capturing phase I & II metabolism
- Correlate drug metabolite production with cell health measurements
- Quantify clearance rates, even for slowly metabolised drugs (5 ml/min/kg)
- Compatible with small molecules, antibodies, viral vectors, ASOs and other new modalities
- Induction, inhibition and drug-drug interaction studies
- Adaptable to model the effects of disease/inflammation on metabolism
- Cultures maintained under flow perfusion using the PhysioMimix™ OOC Microphysiological System
Detecting compounds with varying clearance rates – clearance of disopyramide (yellow) , diclofenac (pink) and phenacetin (green) in LC12 plates
(click image to enlarge)
Predicting human hepatic clearance – comparison of in vivo and liver-on-chip hepatic clearance rates of five common molecules
(click image to enlarge)
Safety Toxicology Testing
To understand causality and mechanistic aspects of drug-induced liver toxicity in great detail, take a step beyond what is currently possible and submit your lead candidates for test against our human liver-on-chip in vitro model.
Maintained under flow perfusion for up to 4 weeks, co-cultures of human hepatocyte and non-parenchymal cells (NPC) form highly functional 3D liver microtissues. Following acute or chronic drug dosing, an almost exponential number of functional liver-specific endpoints can be analysed from the culture medium, liver microtissue, or via non-invasive techniques from which distinct mechanistic “signatures” of hepatotoxicity can be observed. End points include clinical markers that are notoriously difficult to detect in vitro (e.g. AST/ALT).
More complex mechanistic questions can be investigated, using our liver-on-chip model, such as the stratification of different patient populations versus their DILI susceptibility and toxicity profiles, or inflammatory-mediated toxicity. It is even possible to study inter-organ crosstalk and toxicity through use of multi-organ microphysiological systems such as gut-liver, lung-liver or circulating immune cells and liver.
-
Highly functional hepatocyte and NPC co-cultures for up to 4 weeks
-
Compatible with small molecules, antibodies and many new modalities (e.g. viral vectors, ASOs)
-
Report an almost exponential number of functional liver-specific endpoints (inc. LDH, Albumin, Urea, ATP, WST-1)
-
Quantify clinical markers (AST/ALT, miR122)
-
Produce distinct hepatotoxin signatures
-
Detect acute or chronic drug-induced liver injury (DILI)
-
Investigate causality and mechanistic aspects of toxicology
-
Explore inter-organ crosstalk
-
Inflammatory-mediated toxicity
-
Stratification of patient populations
- Cultures maintained under flow perfusion using the PhysioMimix™ OOC Microphysiological System
Detecting human specific toxicant signatures – hierarchical cluster analysis of LDH leakage, albumin secretion and Urea production to assess toxicity of compounds
(click image to enlarge)
Investigating causality – detecting cholestatic injury following treatment with hepatotoxicant
(click image to enlarge)
Related content
WEBINAR
Testing on Humans: How to Predict Hepatotoxicity and Drug Clearance Ahead of Clinical Trials Using Liver-on-a-Chip
APPLICATION NOTE
Microphysiological system for studying fatty liver disease and its impact on drug-induced liver injury
SCIENTIFIC PAPER
Quantitative Assessment of Population Variability in Hepatic Drug Metabolism Using a Perfused Three-Dimensional Human Liver Microphysiological System
SCIENTIFIC PAPER
Perfused human hepatocyte microtissues identify reactive metabolite-forming and mitochondria-perturbing hepatotoxins
SCIENTIFIC PAPER
Characterizing the Reproducibility in Using a Liver Microphysiological System for Assaying Drug Toxicity, Metabolism and Accumulation