ADMET

Our team has outstanding experience and capability to develop fit for purpose ADME and In Vivo rodent and non-rodent pharmacokinetic studies to scientifically support client needs. We have expertise in developing quantitative LC-MS/MS method for complex biomarkers in bio-fluids and tissue samples.

Physiochemical Properties

Aqueous Solubility:

  • Kinetic
  • Thermodynamic
  • Biorelevant media (FaSSIF and FeSSIF)

Lipophilicity (Log D and Log P):

  • Octanol-water/phosphate buffer partitioning

Stability

  • Simulated Gastro Intestinal fluids (SGF, SIF)
  • Biorelevant media (FaSSIF and FeSSIF)
  • Aqueous buffers at different pH
  • Plasma and blood stability
  • Dosing formulation

Pre-formulation

  • Topical formulations
    • Creams/ointment/gel

Metabolism

  1. Metabolic stability/ intrinsic clearance
    • Liver and intestinal microsomes
    • S9 fractions
    • Hepatocytes
    • Direct glucuronidation in liver microsomes using UDPGA
    • Reactive metabolites identification using GSH trapping assay
    • Metabolite finger printing analysis in liver microsomes

  2. Metabolism based drug-drug Interactions
    • CYP inhibition (single point, IC50) using human liver microsomes (HLM)
    • Time dependent CYP inhibition in HLM (IC50 shift, Ki and Kinact)
    • CYP reaction phenotyping (purified rCYPs/microsomes)
    • CYP induction in plateable human hepatocytes
      1. 1A2, 2B6 and 3A4 enzyme activity
      2. mRNA analysis
      3. Cytotoxicity

Permeability/Absorbtion:

  • Intrinsic permeability-PAMPA
  • Mono and bi-directional transport: CaCo-2 and MDCK cells
  • In presence and absence of efflux drug transport inhibitors (P-gp, BCRP and MRP)

Distribution/Binding

  • Definitive plasma protein binding
  • Microsomal  protein binding
  • Brain tissue binding
  • Blood-to-plasma concentration ratio (RBC partitioning)

Cytotoxicity

  • HepG2 cell line
  • Hepatocytes