ADME & in vitro Pharmacology

As discovery lead optimization is a serious bottleneck in drug discovery, Pharmacelsus offers a broad range of beneficial tools for the acceleration of a hit to lead or a discovery lead optimization process.

A drug is subjected to many processes in a body, including Absorption, Distribution, Metabolism as well as Excretion (ADME). With the in vitro ADME services, Pharmacelsus offers reliable data for profiling.

Absorption

Physico-chemical properties

• aqueous solubility
• chemical stability
• lipophilicity by CHI, log P
• stability in biological matrices (blood, plasma, intestinal fluids)

Permeability screening on artificial membranes or cellular systems

• PAMPA (Parallel Artificial Membrane Permeation Assay): prediction of intestinal absorption

• BBB (blood brain barrier): prediction of CNS penetration
• Caco2 cell monolayers (bidirectional)

Membrane transporter assays

• P-glycoprotein (Pgp) interaction
• Characterization of membrane drug transporter interactions (ABC - ATP  Binding Cassette Carrier, SLC- Solute Carrier)
• Hepatobiliary transport studies (cryopreserved hepatocyte sandwich culture)

Distribution

Protein Binding

• Plasma protein binding
• Serum protein binding
• Blood partitioning
• Determination of dissociation constants (Kd) for human serum albumin (HSA) and α1-acid glycoprotein (AGP)

Metabolism

Metabolite stability determination (various species) incl. metabolite characterization

• Microsomes (Phase I and/or II)

• Hepatocytes

Cytochrom P450 (meets FDA guidelines)

• CYP induction (in HepaRG® cell line or human hepatocytes)
• CYP inhibition (evaluation of direct and metabolism dependent inhibition, rapid screen, recombinantly expressed single P450 enzymes, Probe substrate approach with liver microsomes)
• CYP profiling (rapid screen, recombinantly expressed single P450 enzymes, Probe substrate approach with microsomes )