Steven Erpelinck BSc. MBA
- AMS transporters
- PBPK modeling
Contact Steven Erpelinck for more information.
InTESTine™ enables the investigation of the absorption, interaction and translocation of pharmaceutical, biological and nutritional compounds across the intestinal wall. In this physiologically relevant medium-throughput system, fresh ex vivo intestinal mucosal tissue of human or animal origin is mounted into a two-compartment model with an apical and basolateral side.
TNO offers a broad portfolio of drug transporter assays, including cell-based transporter assays (bi-directional transporter assays as well as accumulation assays). We provide a broad range of human and rodent transporter assays in CaCo-2, MDCK, and HEK293 cells, including the ones recommended by the FDA/EMA. Additionally, we can perform LCMS/MS based transporter protein quantification.
I-screen can be used to evaluate the effects of substances (e.g. drugs, nutrients) on the human gut microbiota composition and functioning and vice versa: the effects of human gut microbiota on drug metabolism and reductions. I-screen uses physiologically relevant anaerobic conditions and culture media to mimic human colon microbiota conditions.
Currently available in vitro liver models often fail to predict PK, mainly due to absence of biliary excretion route. TNO has developed an ex vivo liver platform using whole perfused livers of porcine origin. This platform enables the investigation of:
The binding of drugs to plasma proteins has major consequences for their pharmacokinetic properties. Many methods for determining the free fraction of a drug in blood plasma have been described. There is still an unmet need for a highly sensitive PPB assay for hydrophobic and highly binding drugs. For this class of compounds we have developed a competitive partitioning to a polymer phase assay (ComP3). The results of the ComP3 assay are highly reproducible (assay sensitivity: free fraction in human plasma < 0.05%).
TNO has access to two accelerated mass spectrometers (AMS) facilitating microdosing & microtracer studies. 14C-labelled drugs are administered to human volunteers or patients, followed by measuring parent drug and/or metabolites in different matrices (blood, plasma, urine, faeces) as early as possible in clinical development using auto-combustion-based AMS.
Used for candidate selection based on PK characteristics after administration of a microdose (<100ug, < 1uCi) to human subjects.
A classical Phase 1 study, oral administration of a cold therapeutic dose, can be extended with IV administration of a 14C-labelled microtracer at Tmax, to generate absolute bio-availability (AbsBA) at an early stage of development. Additional microtracer studies will generate mass balance and MIST data, thus accelerating and de-risking clinical development.