Drug Metabolism and Pharmacokinetics (DMPK)
The Drug Metabolism and Pharmacokinetics(DMPK) team members possess advanced degrees in relevant specializations from top universities in India and abroad and bring many man years of industrial experience. At Anthem the studies are performed using methods, instrumentation and technologies available with top tier pharmaceutical companies. The studies are carried out in a state of the art facility that includes experimentation labs and a vivarium.In vitro DMPK
PHYSICOCHEMICAL PROPERTIES
- Thermokinetic and thermodynamic solubility (MultiScreen HTS filter plates/ LC-MS/MS method)
- Stability in buffer solutions, simulated gastric fluid and simulated intestinal fluid (Fasted and Fed), in plasma of different species like human, monkey, dog, rat and mouse.
- Log D(7.4) : Shake flask method (n-octanol/cyclohexane: Phosphate buffer saline)
- log P and pKa determination
DISTRIBUTION
- Plasma Protein binding determination by Ultrafiltration method and Equilibrium dialysis
- Species: human, monkey, dog, rat and mouse
- In-vitro tissue binding
- Blood cell partitioning
- Microsomal binding
ABSORPTION / PERMEABILITY
- PAMPA (Parallel Artificial Membrane Permeability Assay)
- MDCK-wild type permeability
- MDR1-MDCK permeability for P-gp interaction
- Caco-2 permeability
- a. Unidirectional permeability (Single or Multiple time points)
- b. Bidirectional permeability (Single or Multiple time points): with and without Pgp inhibitor
- Calcein AM assay for P-gp interaction and inhibition
METABOLISM
- Metabolic stability in liver, intestinal microsomes, S9 fractions and hepatocytes
- Metabolite identification (phase I and II) and characterization studies using LC- MS/MS
- Species: rat, mouse, monkey, dog and human
- Hepatocyte stability
In vivo PHARMACOKINETICS
SPECIES
- Rat
- Mouse
- Hamsters
- Guinea pigs
- Rabbits
TYPES OF PK STUDIES
- Single dose
- Multiple dose
- Cross over
- Cassette dose
ROUTES
- Oral
- Intravenous
- Subcutaneous
- Intradermal
- Intramuscular
- Intraperitoneal
- Per rectal, etc.
TISSUE DISTRIBUTION STUDIES (ORGANS)
- Brain, liver, adipose, skin, muscle, spinal cord, etc.
PHARMACOKINETICS STUDY IN DISEASE MODELS
- Cancer models eg. tumor bearing athytymic animals
- Diabetes models eg. db / db mouse
- Obesity models eg. Ob/ob mouse, DIO mouse
- Inflamation models eg. IBD model, arthritis model
- Tissue distribution in efficacy models and PK-PD correlation
EXCRETION
- Biliary excretion in rats
- Renal excretion in rats
PHARMACOKINETICS DATA ANALYSIS
- WinNolin (Pharsight)
- Parameters reported: Tmax, Cmax, AUClast, AUC∞, Cl, t1/2, Vss, MRT and F%
- Plasma to tissue ratio
BIOANALYTICS
- Method development and validation
- Development of efficient/reproducible extraction procedures (protein precipitation, liquid- liquid extraction, solid-phase extraction)
- Recovery and linearity studies
- Development of analytical methods in Biological Matrix - plasma, serum, bone marrow, lymph node, urine, feces, bile, other tissues, samples from both in vivo and in vitro studies
INSTRUMENTATION
- HPLC (PDA, Fluorescence), LC-MS-MS - Triple quad and QTrap
Integrated Discovery
Facilities