Pharmacology
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]