Preclinical (DMPK) studies

In Vitro ADME

• Aqueous solubility and stability of the compounds at different pH, Stability of the compounds at ambient temperature, 2-8/-20°C
  Short term and long-term stability of the compound in biological matrices(plasma/serum) Metabolic stability studies using cellular (hepatocytes from rat, mouse, human etc) and sub cellular fractions, metabolic stability studies recombinant CYP isoforms such as CYP3A4, CYP2C9, CYP2C19, CYP2D6 and CYP1A2
• Cell permeability assays – PAMPA, MDCK, and CaCo-2
• Plasma/serum protein binding by ultrafiltration / equilibrium dialysis technique

In-Vivo DMPK services

• Pre-formulation development
• Absolute Bioavailability studies
• Single, Multiple and cassette dosing
• Ascending dose PK in rodents
• PK studies in cannulated and non-cannulated rodents

In vivo models

• Inflammatory pain: CFA, Carrageenan, Capsaicin, Formalin models, collagen-induced arthritis
• IBD: DSS induced colitis in mice, TNBS induced colitis in rats
• Respiratory: Rodent models of LPS-induced neutrophilia and ovalbumin induced eosinophilia
• Cytokine Release Models: Mouse models of LPS induced
• TNF α and IL-1 release, rat model of ATP activated IL-1β release
• Acute and Chronic OGTT, IPGTT models (glucose & insulin)
  DIO mouse model (pair fed studies)
• Acute model for GLP-1 induced Incretin secretion & endocrine secretion (PYY / CCK)
• Acute model for Malonyl CoA lowering

Pharmacokinetics

Skanda conducts regular preclinical PK studies and can customize based on clients’ requirements.

Species used – Rat, Mice, Rabbit, Guinea Pig, Hamster, Nude mice, Swine

• Typical animal PK study by various routes viz oral, intravenous (bolus and infusion), intraperitoneal, sub-cutaneous
• Single, multiple and cassette dosing of compound(s)
• Dose escalation study (dose linearity and range finding)
• Tissue distribution study (brain, heart, liver, lung, kidney, Eye etc.)
• Determination of fundamental PK parameters (Tmax, Cmax,
• AUC, clearance, oral bioavailability, volume of distribution, etc.)
• Blood brain barrier & PK-PD Evaluation

In vitro screens / Cell / Ex-vivo assays

• Cytokine Release Assays (IL-1b, IL-6, IL-8, TNFα, IFNγ, etc.) from macrophage and T cells
• Myeloperoxidase, Eosonophil peroxidase and nitric oxide
• assays in monocyte-derived cell lines
• Chemotaxis assays in primary thymocytes and T-cell lines
• Kinase and STAT phosphorylation assays
• Cytokine-induced IFN γ release in whole blood
  IKK/NF-kβ Assays
• T cell proliferation assays
• Incretin and Insulin Secretion Models; Adipogenesis and Adipolysis models; Apo B secretion model [Hepatocyte]; Fatty acid oxidation model [Skeletal muscles]; Membrane potential assays [myocytes, hepatocytes]