In Vitro/In-Vivo ADME

At Intonation, we carry out in-vitro and in in-vivo pharmacologic and physicochemical property analysis of biologically active small molecules to support drug discovery projects. We feature the assessment and optimization of Structure-Pharmacological / Property-Relationships (SPR), which may be a critical step for efficacy evaluation.

Additionally, to assess compound characteristics like solubility, protein binding, permeability, stability etc. our teams prioritize different structural classes and order them not only on potency but also in reference to potential downstream absorption or metabolic liabilities.

In-vitro – Physico-chemical characterization, cell and non-cell-based absorption, metabolism (microsomes/hepatocytes), CYP isozymes.

in vitro

In-vitro ADME Screening:

Aqueous Solubility: Kinetic, Thermodynamic, Thermodynamic equilibrium solubility in water, organic solvents, buffers, formulations solvents.

Lipophilicity: LogP/LogD

Metabolic Stability: Rat, mouse, dog, human microsomes, Cryopreserved hepatocytes

Drug-drug interaction: CYP450 inhibition or CYP450 induction

Distribution: Plasma protein binding, Blood partitioning, PAMPA/Caco-2 permeation studies

Plasma stability and Plasma Protein binding: (Mouse, Rat, Dog and Human), Stability in SGF and SIF

CYP Inhibition (1A2, 2C8, 2C9, 2C19, 2D6, 3A4): both % inhibition and IC50, Time-dependent CYP inhibition

In-life Pharmacokinetics – Bioavailability, blood-brain barrier, cerebrospinal fluid, tissue distribution, etc. in rodents. Our In-vivo services include exploratory PK, PD and TK studies. Understanding the bioavailability, exposure, half-life, clearance and metabolism of a drug may be the difference between success and failure in the clinic. We provide in vivo dosing and sampling in rodents, PK bioanalysis, and report preparation.

  • Routes of Administration - Oral (PO), Subcutaneous (SC), Intravenous (IV), Intramuscular (IM), Intraperitoneal (IP), Dermal
  • Multiple Dosing regimen- Single/Multi Dose and IV cassette PK in mouse and rat
  • Collection from - Whole blood serum, plasma, urine, faeces and tissue (including the brain)
  • Delivery Timelines - Initial results from PK studies will be available in 3-5 days and data will be posted in our secure web portal for immediate client access.

Bioanalytical Lab Services:

  • Pharmacokinetics (PK) Studies, PK Sample Analysis, Toxicokinetics (TK) Studies, Rapid PK Screening, Mass Balance, Tissue Distribution, Bioequivalence (formulation support), MSD-ECLA (Meso Scale Discovery) Assays, ELISA Assays
  • Metabolite ID and kinetic studies- including metal bowl studies, radiolabel studies: 14C, 3H and 125I