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.

ADME

Absorption

Physico-chemical parameters

  • aqueous solubility
  • chemical stability
  • storage 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)

Interaction with drug transporters

  • P-glycoprotein (Pgp) interaction
  • Characterization of membrane drug transporter interactions (ABC - ATP  Binding Cassette Carrier, SLC- Solute Carrier) (partnered service)

Distribution

Protein Binding

  • Plasma protein binding
  • Serum protein binding
  • Microsomal protein binding 
  • Brain tissue binding
  • Blood partitioning
  • Determination of dissociation constants (Kd) for human serum albumin (HSA) and ?1-acid glycoprotein (AGP)
  • Reactive metabolite trapping

Metabolism

Metabolic stability determination (all preclinically relevant species)

  • Microsomes (Phase I and/or II)
  • Hepatocytes (Phase I and/or II)

Cytochrom P450 (according to FDA + EMA guidelines) interaction

  • CYP inhibition (evaluation of direct and metabolism dependent inhibition, rapid screen, recombinantly expressed single P450 enzymes, probe substrate approach with liver microsomes)
  • CYP phenotyping (recombinantly expressed single P450 enzymes)

Metabolic pathway identification

  • hepatocytes
  • subcellular fractions