Jubilant Biosys

Delivering the Added Dimension in Drug Discovery Services

DMPK

Drug Metabolism and Pharmacokinetics (DMPK) is an integral part of drug discovery. Its central role is to contribute to the optimization of novel chemical entities in drug discovery by balancing the properties associated with drug gastrointestinal absorption (for orally delivered therapies), distribution, clearance, elimination and DDI potential as rapidly and cost-effectively as possible.

The DMPK department comprises in-vitro, in-vivo, metabolite ID and pre-formulation groups, managed by highly experienced and matured scientists. We guide discovery projects by troubleshooting scientific issues and offer changes on scaffolds to drive discovery projects in the right direction and de-risk failures in the later stage of development due to DMPK related issues.

DMPK Services

Jubilant’s DMPK technical and research services meet the highest standards of professional performance to satisfy the unique requirements of our clients. Our team supports both integrated pre-clinical discovery programs and fixed-fees-for-services (FFS) projects and delivers quality and reproducible results with quick turnaround time. We work closely with our clients to identify their needs and clarify their expectations, including cost and time constraints.

In-vitro ADME Services

The team provides in-vitro ADME services (absorption, distribution, metabolism and excretion) with the expertise to guide discovery projects from hit identification, through hit to lead optimization, and then lead optimization up to the identification of clinical candidates. To reduce the chance of failures in development, we troubleshoot and offer changes on scaffolds for a quick go/no-go decision at the discovery stage.

In-vitro ADME Screening

The team has a track record to carry various in-vitro studies or in-vitro ADME screening at various stages of the drug discovery and development process to flag potential issues such as:

  • Physiochemical studies – Kinetic solubility, thermodynamic solubility in PBS, SGF, SIF, chemical stability, early formulation assessment, etc.
  • In-vitro metabolism services – Metabolic stability using liver microsomes/hepatocytes/rCYPs/S-9 fraction, CYP inhibition, CYP phenotyping and CYP induction (using PXR cell lines), CYP profiling to understand the involvement of CYP enzymes, blood/plasma/brain/tissue/microsomal protein binding, stability in plasma, buffer, blood, blood/plasma ratio, GSH adduct, TDI, etc.
  • In-vitro permeability and transporter studies – PAMPA, MDR 1-MDCK/Caco-2 permeability, inhibition and substrate assessment of P-gp and BCRP transporters.

In-vivo Studies

  • PK studies by various routes (oral, intraperitoneal, intravenous, subcutaneous, etc) in mice, rats, rabbits, hamsters, guinea pigs and dogs (dogs in-life phase will be outsourced to a third party), dose range finding studies, brain exposure study, etc.
  • Tissue distribution
  • Excretion study
  • Biliary and urine excretion study

The DMPK team has published several research articles in peer-reviewed international journals and presented posters in conferences.

ADME Surrogates

Physicochemical Properties

  • Solubility (thermodynamic and kinetic method)
    • Various pH
    • Biorelevant medium (FaSSIF, FaSSGF, FeSSIF)
  • Chemical stability
  • Blood partitioning

In-vitro Permeability

  • PAMPA
  • Caco-2
  • MDCK (wild type)
  • MDCK-MDR1

Animal Pharmacokinetics

  • Pharmacokinetics by various routes, viz. oral, intravenous, intraperitoneal, subcutaneous in mice (Swiss Albino, C57/BL, Balb/C), rats (Wistar, Sprague Dawley), rabbits (New Zealand White), Guinea pigs (Golden Syrian) dogs (Beagle), etc.
  • Ocular PK studies in rats and rabbits
  • Tissue distribution
  • Brain to plasma ratio
  • Biliary and urine excretion
  • Mass balance

Protein Binding

  • Plasma protein binding (ultra-filtration and equilibrium dialysis)
  • Microsomal protein binding

 In-vitro Metabolism

  • Cytochrome P450 inhibition
  • Cytochrome P450 time dependent inhibition
  • Metabolic stability
    • Liver microsomes
    • S-9 fraction
    • Cryopreserved hepatocyte
  • Plasma stability
  • GSH trapping

Metabolite ID

  • Identification of in-vitro (microsomes, S9 and hepatocytes) and in-vivo samples (plasma, bile, urine, etc.)