DMPK Services

GVK BIO offers a broad range of DMPK services to support Drug Discovery and Development needs of Pharmaceutical and Biotechnology companies across the globe. We provide cost efficient and customised assays as per the client’s requirement. We have capabilities to conduct Drug ability, Drug Metabolism and Pharmacokinetics Assessment from Target to IND filing. We work with the objective that no development candidate should fail in the clinic due to an unforeseen efficacy or metabolic or pharmacokinetic or toxicity properties.

We have a team of highly trained In Vitro and In Vivo PK scientists with extensive global drug discovery experience. Excellent client communication with collaborative and flexible approach facilitates rapid and sound decision making in your drug discovery endeavours.

Assessment of Physiochemical & In Vitro ADME Properties

• In silico properties
• Solubility
• Log D
• Microsomal stability
• CYP inhibition

Optimisation of Physiochemical & Druggable Properties

• Metabolic stability
• CYP inhibition
• Permeability
• Plasma protein binding
• In vivo PK (rodent)
• Reactive metabolite

Optimisation of Druggable Properties, IVIVC, PK/PD Correlation

• Permeability
• Plasma protein binding
• PK (rodent)
• PK (non-rodent)
• Target tissue exposure
• Blood/plasma partioning
• IVIVC, renal/biliary CL
• Mass balance
• PK/PD
• Met id (soft spot)

Dose Range Finding, Safety/Tox Assessment, Interspecies Scaling

• Dose range finding (rodent and non-rodent)
• PK/PD
• Tissue distribution
• Food effect
• Metabolite profiling
• Safety profiling
• Toxicokinetics
• CYP induction
• Interspecies scaling

Physicochemical Characterisation

For drugs to be effective they must be able to reach their targets in efficacious concentrations.

A number of physicochemical parameters obtained in the following assays are used to assess the potential utility of compounds
as therapeutic agents:

  • Aqueous solubility (pION, Kinetic and Thermodynamic)
  • Partition coefficient (log D) BBB and GIT
  • Ionisation constant (pKa) with spectrophotometer
  • Chemical stability

Absorption/Transporters

The preferred route of drug delivery is oral administration. Intestinal membrane permeability is a critical characteristic that determines the extent and rate of drug absorption and ultimately affects the bioavailability. The human colon adenocarcinoma cell line, Caco-2, and Madin-Darby canine kidney cell line, MDCKII, are used as an alternative in vitro permeability model. PAMPA (parallel artificial membrane permeability assay) is also used to determine the passive permeability of the compounds.

Permeability/Transporters:

  • PAMPA: GIT/BBB/skin
  • Caco-2 (Pgp efflux)/MDCK permeability/BCRP
  • Skin and buccal permeability by Franz Diffusion Method
  • Ongoing Developments
  • MDCK -Transfected ABC transporters (stable cell lines)
  • SLC transporters: OATP1B1, OATP1B3 and OCT1 (Hepatic)
  • OAT1, OAT3 & OCT2 (Renal)

Distribution

Protein Binding
The free drug concentration is more closely related to the activity of the drug than the total plasma concentration. Drugs with low protein binding have a large volume of distribution and they can equilibrate rapidly with tissues. High protein binding causes a small volume of distribution, slow equilibration with tissues, and are usually a predictor of elimination by metabolism. We employ Rapid Equilibrium Dialysis approach to measure plasma as well as other matrices protein binding taking Warfarin as the reference control.

Blood Partitioning
Knowledge of the partitioning behaviour of a therapeutic compound into red blood cells is important to the interpretation and understanding of a compound’s pharmacokinetic profile. A high partitioning ratio may also lead to the accumulation of the compound in red blood cells and therefore, this parameter serves as an indicator of potential hematotoxicity. We use fresh blood to conduct this study taking chloroquine as the reference control.

Metabolism

Metabolism studies are useful in:

  • Determining the initial rate at which compounds are metabolised
  • Investigating the major pathways of drug metabolism
  • Predicting in vivo pharmacokinetic properties
  • Investigating the potential for drug-drug interaction

At GVK BIO, we conduct the following assays:

  • Metabolic stability in interspecies using S9, microsomes or hepatocytes
  • Drug-drug interactions
  • CYP inhibition
  • Reaction Phenotyping
  • Reactive Metabolites (CN and GSH trapping)

Pharmacokinetics Studies

GVK BIO has the capability to conduct all types of studies related to Pharmacokinetics of BCS 1 to BCS 4 classes of compounds. On an average about 450 to 500 different PK studies are conducted in rodents (mice, rats, guinea pigs and rabbits) and non-rodents (Beagle dogs). We have expertise in difficult surgeries in mice (Cerebrospinal fluid, Bile and Bronchoalevolar Lavage collection).

Pharmacokinetics Work Flow:

Pharmacokinetics Capabilities:

Accreditations, Compliance & Quality Systems:

Certification and Compliance

  • AAALAC accredited rodent vivarium facility
  • In house facility for rodent equipped IVC cages
  • Regulatory
    • PHS-NIH approved animal facility
    • OHSAS (Occupational Health & Safety Assessment Series)
    • Institutional Animal Ethics Committee (IAEC) constitute to an external member and CPCSEA nominee
    • Protocols of experimentation study are approved by IAEC and reviewed by the committee
    • Bio-waste Disposal Management registered under State Pollution Board
    • EMS (Enviornment Management System as per ISO 14001)
    • In life part of large animal PK study with collaborator
    • Approved Radioactive facility and In House Radiation Safety Officer appointed by AERB
    • Radiation Safety Committee to monitor Radioactive material use and disposal
    • Approved by Institutioal Bio Safety Committee

Quality System

  • Procurement of animals from certified vendors
  • Documentation of animal health status at receipt
  • Subjecting all newly arrived animals to quarantine
  • Physical examination of animals by veterinarian
  • Subjecting animals for clinical tests:
    • Parasitological examination
    • Haematological
    • Biochemical
    • Microbiological examination of faeces for pathogenic organisms on blood agar
    • Feed, water and bedding material analysis
  • Ethical efforts to avoid pain and distress to animals subjected to experimentation
  • Anesthesia and euthanasia as per CPCSEA guidelines

Mass Balance Studies

We perform mass balance with non-radiolabeled compounds. We can collect 49 different tissues after perfusion from animals following PK studies.

Other Specialised Assays

GVK BIO offers highly customised and cost effective assay development services. Our scientists are well-versed with development of need-based assays in the most economical way.

  • CYP induction
  • GSH trapping
  • Cyanide trapping
  • Metabolite(s) identification
  • Soil metabolite(s) identification

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