Drug Metabolism and Safety Toxicity Testing Services

Take a step beyond what is currently possible and improve your chances of clinical success through our fast-track services.

Our advanced 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

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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

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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. The latter can and does put clinical programs on hold.

By testing your lead candidates against our human liver-on-chip model, the the risk of an unexpected surprise is reduced. Compatible with a wide variety of different drug modalities our cultures produce a range of phase I and II human drug metabolites at different rates. These can be identified in temporal (repeat sampling) studies using LCMS analysis. Furthermore, cell health measurements can be made from the same sample, enabling direct correlations between metabolite formation and toxicity to be extrapolated.

With high metabolic activity maintained for weeks, it is also possible to differentiate and quantify a wide range of clearance rates, including slowly metabolised drugs.

  • 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

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Predicting human hepatic clearance – comparison of in vivo and liver-on-chip hepatic clearance rates of five common molecules

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In vitro In vivo extrapolation – population-based PK model of Lidocaine clearance

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Safety Toxicology Testing

With safety concerns being the principal cause for failures in phases 1 and 2 of clinical trials, it is clear that we need more predictive models within drug discovery and development to improve translatability. Focus has turned to human in vitro 3D liver models to provide the solution.

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

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 Investigating causality – detecting cholestatic injury following treatment with hepatotoxicant

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Patient stratification – comparing healthy and fatty liver-on-chip models susceptibility to drug-induced liver injury

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Related content

WEBINAR

Testing on Humans: How to Predict Hepatotoxicity and Drug Clearance Ahead of Clinical Trials Using Liver-on-a-Chip

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APPLICATION NOTE

Microphysiological system for studying fatty liver disease and its impact on drug-induced liver injury

Download booklet

SCIENTIFIC PAPER

Quantitative Assessment of Population Variability in Hepatic Drug Metabolism Using a Perfused Three-Dimensional Human Liver Microphysiological System

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SCIENTIFIC PAPER

Perfused human hepatocyte microtissues identify reactive metabolite-forming and mitochondria-perturbing hepatotoxins

Download paper