ADME/DMPK

Here at PTL we provide a broad portfolio of in vitro and in vivo assays that enable evaluation of critical ADMET parameters for pharmaceutical drug discovery.

ADMET Assays

  • Physico-chemical properties – aqueous solubility, pH stability, Lipophilicity (Log D) and Log P
  • Absorption – PAMPA, CaCo-2 and MDCK, Efflux (CaCo-2)
  • Metabolism & stability – Liver microsomes (%PCR and Clint), plasma and serum stability, CYP450 inhibition includes inhibition screening (Fluorescence based/LC-MS/MS based) and time – dependent inhibition (TDI), CYP450 phenotyping and metabolite identification (LC-MS/MS) (in vitro & in vivo)
  • Distribution – plasma protein binding, brain protein binding and blood-plasma distribution (Ce/Cp)
  • Cytotoxicity – cell-based assays in human cell-lines

PK Studies

Early stage PK evaluation of NCE’s in rodents:

  • Biodistribution of fluorescent–products (range 590-702 nm)
  • Discrete and cassette dosing
  • Tissue distribution
  • Brain-plasma distribution
  • Cardiac safety e.g.:
    • Ex vivo: cardiac action potential (cAP) on isolated guinea pig cardiomyocites.
    • In vivo: QT measurements on anaesthetized guinea pig
  • Entero-hepatic recirculation (EHC)
  • Determination of fundamental PK parameters (Tmax, Cmax, AUC, clearance, oral bioavailability, volume of distribution, etc.)

Bioanalysis

  • Development of bioanalytical methods to support bioavailability and pharmacokinetics studies.
  • HPLC -UV and LC-MS/MS based methods
  • Development of efficient extraction procedures (protein precipitation, liquid-liquid extraction, solid-phase extraction)
  • Development of analytical methods in presence of different matrices