How to more accurately predict human drug bioavailability?
Accurately predicting the bioavailability of drugs in humans during preclinical development is necessary to set safe and effective doses in the clinic.
Extrapolating PK parameters from animals to humans during drug development is challenging. The overall correlation between animal and human bioavailability is poor mainly due to differences in physiology and metabolic capacity.
Insufficient bioavailability in humans requires an increase in drug dose to be effective, but this comes with an increased risk of toxicity and side effects.
Our solution
We have developed the PhysioMimix® multi-organ Gut/Liver-on-a-chip, which recapitulates the structure and function of the human tissues and their fluidic interaction, for comparing intravenous and oral compound dosing. Used in the PhysioMimix Bioavailability Assay, this model uniquely recreates the combined effect of intestinal permeability and first-pass metabolism by the liver for the prediction of human oral bioavailability.
Our assay provides robust preclinical data to help to overcome poor animal model bioavailability predictions and validate in silico PBPK modeling for more informed decision-making ahead of clinical trials.
Take a tour of our bioavailability animation
Studying drug bioavailability
Limitations with current techniques
- Animal models fail to accurately predict human bioavailability
- Animal models have varying expression levels for enzymes that drive drug metabolism in humans
- Simple in vitro models cannot model the systemic effects of the drug
- In silico models are dependent on quality input parameters that rely heavily on early in vitro and animal studies
Advancements with PhysioMimix OOC
- Enables the direct, accurate measurement of bioavailability using a human-relevant system
- Perfusion of microtissues promotes the metabolic capacity of cells
- Allows the combined effects of intestinal permeability and human liver metabolism to be explored
- Data derived using a human-relevant approach better informs in-silico models
End point measurements
Longitudinal and endpoint measurements include (but not limited to):
Liver: Functionality biomarkers
- Cytochrome P450 enzyme activity
- Albumin production
- Urea production
- Lactose dehydrogenase (LDH) release
Gut: Functionality biomarkers
- Trans epithelial electrical resistance (TEER)
- Lucifer yellow or dextran permeability assay
- Lactose dehydrogenase (LDH) release
Profiling analysis
- Media samples send to LC/MS for bioanalysis
- Drug concentration over time
- Prediction of human oral bioavailability
- Parent drug clearance
- Known metabolite production
- Area under the curve estimation
- Quantitative PCR assessment of Cytochrome P450 enzyme functionality
Optional profiling analysis
- Quantitative PCR
- Transcriptomics
Modeling an orally administered drug’s route of entry
Uniquely recreate the combined effect of intestinal permeability and first-pass metabolism in vitro using a multi-organ Gut/Liver-on-a-chip for predicting human oral bioavailability.
Improve bioavailability predictions with an in vitro alternative to animals
Oral and IV dosing regimens can be simulated on the multi-organ gut/liver model to provide a better prediction than animal studies of human bioavailability.
Access our ADME Service
Get instant access to PhysioMimix Bioavailability Assay via our CRO Service. Through a collaborative approach, our experts work with you to plan and execute your study.
Standard and bespoke projects are carried out by our dedicated team of scientists in our CRO facility providing you with actionable data within weeks.
Add PhysioMimix OOC into your lab
Harness the power of PhysioMimix OOC in your own lab with the purchase of a single- or multi-organ microphysiological system.
With a growing community of users and support from our experts, there has never been a better time to transition into 3D cell culture.
