enquiry@advinus.eurofinsasia.com
Menu

DMPK

Home / Services / DMPK

Eurofins Advinus offers a wide range of DMPK services to support lead optimization and preclinical development. Eurofins Advinus capabilities and track record include:

  • Highly qualified scientists trained in premier universities in India and abroad
  • Performed over 500 PK studies, 5000 in vitro studies; supported over 200 Toxicology studies for regulated bioanalysis and toxicokinetics
  • Bioanalytical team has developed over 120 validated methods for NCEs, supported over 90+ complete IND packages

A list of the assays and studies that can be performed is provided below.

In-vitro DMPK Assays

in vitro potassium release assay for liposomal formulations of Amphotericin B
in vitro potassium release assay

  • Assay performed with blood from preclinical species or with human blood
  • Achieved dose- and time-dependent potassium release from red blood cells
  • Assay validated for determination of potassium concentration using ICP-MS platform
  • Assay conducted in compliance with GLP and in non-GLP format

Physicochemical Properties

  • Aqueous solubility and stability at different pH condition
  • Stability in simulated gastric and intestinal fluid
  • Octanol water partitioning (Log P and Log D)
  • pKa determination

Permeability 

  • PAMPA
  • Caco-2 cell line
  • MDCKII cell line

P-gp Substrate and Inhibition Potential

  • Caco-2 cell line
  • MDCKII-P-gp transfected cell line

Metabolic Stability

  • Stability in S9, microsomes and hepatocytes to assess potential for intestinal first pass, intrinsic clearance to evaluate in vitro clearance

Plasma Protein Binding

  • Equilibrium dialysis and ultrafiltration techniques
  • Blood/Plasma Partitioning and Stability

Tissue Homogenate Binding

CYP Reaction Phenotyping

  • Using recombinant human CYPs as well as human liver microsomes
  • Aldehyde oxidase reaction phenotyping

Metabolite Identification

  • Using unlabeled and radiolabeled compound coupled with mass spectrometric detection
  • Preliminary metabolite identification
    • In in vitro and in vivo study samples
    • Reactive metabolite trapping and characterization

Drug-Drug Interaction Assays

  • CYP Inhibition using human liver microsomes (IC50, Ki determination)
  • Time dependent CYP inhibition (IC50shift)
  • CYP induction in human hepatocytes
  • P-gp substrate and inhibition assays using Caco2 and MDCKII-P-gp cell lines

Cytotoxicity

  • MTT Assay

In vivo PK studies

In vivo Rodent Pharmacokinetic Studies

Study types

  • Absolute bioavailability
  • Comparative PK
  • Salts / Formulation screening
  • Blood brain barrier evaluation
  • Tissue distribution
  • Cassette PK
  • Routes of excretion
  • Bile duct cannulated animals
  • Excretion in urine and feces
  • Radiolabelled studies

Species / Test systems

  • Mouse
  • Swiss albino
  • CD1
  • C57BL6
  • BALB/c
  • Rat
  • Sprague Dawley
  • Wistar
  • Rabbit
  • New Zealand white
  • Guinea pig
  • Hamster
  • Golden Syrian
  • Beagle dog & Mini Pig
  • PK studies in Goettingen minipig and beagle dog. In-life phase at partner facility

Surgical capabilities

  • Jugular vein
  • Femoral vein
  • Carotid artery
  • Portal vein
  • Bile duct cannulations

Route of Administration

  • Oral
  • Intravenous
  • Subcutaneous
  • Intraperitoneal
  • Intratumoral
  • Intramuscular
  • Intratracheal
  • Intradermal
  • Intravesical
  • Intrathecal
  • Intravitreal
  • Intracolonic
  • Orally Capsule
  • Osmotic pumps; SC/IP
  • SC pellet implantation
  • Test item in feed or water
  • Bladder infusion

Others

  • Formulations for PK studies
  • Bioanalysis by LC-MS/MS (Fit-for-purpose)
  • Phoenix WinNonlin® for PK estimations
  • Scaling of preclinical PK to predict human PK
  • Prediction of starting and efficacious human doses

In vivo 14C labeled DMPK Studies in rodents

  • Mass Balance / Excretion balance
  • Tissue distribution
  • Ocular PK study in rabbits
  • Biliary excretion study
  • Metabolite profiling

Translational drug development or Toxicokinetics

  • Toxicokinetic data analysis and report preparation to support IND enabling studies
  • Allometric scaling: FIH dose projections and human PK predictions
  • Validated Phoenix WinNonlin® software

Formulation Development for PK Studies

Ideally a lead compound should have > 30% oral bioavailability and < 30% liver blood flow clearance and an adequate half-life for once daily dosing. In the absence of this, to improve bioavailability, a suitable formulation needs to be developed. Eurofins Advinus has the capability to execute the following:

  • Development of solution formulation for IV and PO studies of low solubility lipophilic compounds for conduct of preclinical PK studies using
    • pH adjustment
    • Co-solvents
    • Inclusion complexes (cyclodextrins)
  • Attempts are made to achieve formulation using excipients acceptable for use in repeated dose studies
  • The prepared formulations are assessed for accuracy using HPLC or LC/MS/MS method
  • If necessary, salt forms or pro-drugs can be considered for improving the bioavailability of lead compound along with micronization of compound

Formulation Analysis for Toxicological Studies

  • Formulation method development and validation for preclinical dose formulation sample analysis