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.
- 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
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.)
- 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