Early in vitro ADMET Assessment
Bertin Pharma offers a comprehensive range of services for early in vitro ADME assessment, as well as for drug metabolism studies, to assist you after the drug discovery for the lead selection.
In vitro ADME studies performed by Bertin Pharma are summarised in our Early in vitro ADMET assessment flyer.
Our Solutions to Various Issues:
- cell permeability in models such as Caco-2 cells, MDCK cells, human Blood Brain Barrier models, along with the study of efflux transporters possibly involved in the passage through these natural barriers
- plasma protein binding (Rapid Equilibrium Dialysis, ultrafiltration)
- transporter inhibition or induction using the P-gp drug interaction model or various cell-based models coupled with bioanalytical methods allowing to quantify gene expression (RT-qPCR), protein amount (MS2PLex) and biological activity. Certain studies are performed according to the FDA recommendations
- CYPs inhibition/induction/down-regulation in liver microsomes, primary hepatocytes or rec.hCYPs P450 marketed worldwide by Bertin Pharma (protein amount & activity)
- interspecies comparative metabolic profiling
- Drug-Drug Interactions (DDI)
- identification of P450 pathways & determination of kinetic parameters
- metabolomic approach for metabolism studies
- drug clearance, tissue stability on hepatocytes or subcellular fractions (microsomes, S9 fractions), intestinal cells, keratinocytes, fibroblasts & Peripheral blood mononuclear cells (PBMC)
For multifunctional/complex molecules, we also offer our Biotransformation Technology to produce Phase I & Phase II metabolites using micro organisms or genetically modified yeast over-expressing human CYP 450 .
Quick & Reliable Bioanalysis Methods
For Bioanalysis applied to in vitro ADME, the main challenges for Bioanalysis within in vitro ADME studies are:
- to have generic methods whose implementation is quick, applicable to the larger number of molecules while maintaining specificity, reliability & robustness without fully GLP compliance and;
- to have methods to measure the activities or quantify enzymes or transporters
- to master the determination and quantification of metabolites.