Corporate Headquarters: Phone: +91-40-6677-7555
Email: info@sailife.com

DMPK Services

In vitro DMPK

High quality ADME data is essential to identify and helpaddress issues rapidly and early in the drug discovery, lead validation and optimization processes. The in vitro ADME screening service offers a portfolio of assays for investigating physicochemical properties, permeability, metabolism, drug-drug interactions (CYP inhibition, induction and phenotyping) and protein binding. These assays are offered either as a standalone servicesor to support our client sponsored medicinal chemistry programs.
  1. Physicochemical properties
    1. Aqueous Solubility
      1. Kinetic
      2. Thermodynamic
      3. Simulated GI fluids (SGF, SIF, FaSSIF)
    2. Acid dissociation constant (pKa)
    3. Lipophilicity (LogP/LogD)
      1. Using GLpKa instrument
      2. Shake flask method
    4. Stability
      1. Simulated GI fluids (SGF, SIF, FaSSIF)
      2. Aqueous buffers at different pH
      3. Plasma and blood stability
  2. Permeability / Absorption
    1. PAMPA
    2. Caco-2
      1. Mono directional
      2. Bidirectional
      3. With and without Pgp inhibitor
    3. MDCK
    4. MDCK-MDR1 (in progress)
  3. Metabolism
    1. Metabolic stability / intrinsic clearance
      1. Microsomes (alone and also using UDPGA and alamethacin)
      2. S9 fractions
      3. Heptaocytes
    2. Drug-Drug interaction (DDI)
      1. Competitive CYP inhibition (single concentration, IC50and Ki)
        1. Human liver microsomes
        2. Human recombinant enzymes
      2. Mechanism based inhibition (MBI) (IC50, Ki and Kinact)
      3. CYP induction (in progress)
      4. CYP phenotyping
        • Human liver microsomes using specific chemical inhibitors
        • Human recombinant enzymes
  4. Metabolite identification and biotransformation
    1. Identify stable metabolites using LC-MS Q-trap fragmentation patterns
    2. Identify reactive metabolites using GSH trapping assay and neutral loss by LC-MS
    3. Covalent binding assays with radiolabeled compounds
    4. Direct glucuronidation in human liver microsomes fortified with UDPGA
  5. Distribution/binding
    1. Plasma protein binding species comparison
    2. Microsomal protein binding
    3. Brain tissue binding
    4. Blood-to-plasma ratio (RBC partitioning)

In Vivo Pharmacokinetics

We at SAI Life Sciences can perform in vivo animal pharmacokinetic (PK) and other ADME studies in a mouse and ratin our CPCSEA approved AAALAC-accredited animal facility. We have a third party collaboration (CPCSEA approved facility) to perform pharmacokinetic studies in dogs.

A quantitative measure of drug exposure is necessary in order to interpret preclinical efficacy and toxicity studies. In a typical animal PK study, blood samples are obtained from animals at different time points following a single dose of a test compound. Plasma is harvested and subjected to bioanalysis. In an absolute bioavailability study of an orally administered drug, both oral and IV PK has to be performed. Relative oral bioavailability studies with different formulations can be carried out to enable selection of appropriate preclinical formulation for any compound. In toxicology studies, a satellite toxicokinetics group is included so as to assess the NOAEL (No Observable Adverse Effect Level) for any compound.

Turnaround time

  • Ten working days from the receipt of compound
  • Bolus IV
  • IV infusion
  • Intraperitoneal
  • Oral
  • Intra-dermal
  • Subcutaneous
  • Intra-nasal
  • Blood/plasma/urine/feces
  • Bile
  • Cerebrospinal fluid
  • Tissues like intestine, colon, liver, lung  and kidney,

In Vivo Dosing

Biological Matrices

  • Blood/plasma/urine/feces
  • Bile
  • Cerebrospinal fluid
  • Tissues like intestine, colon, liver, lung and kidney

Service Offerings

  • IV infusion PK for conscious rat
  • Single, multiple and cassette dosing of compound(s)
  • Enterohepatic recirculation in rat
  • Metabolite Characterization & Identification of in vivo samples
  • Dose escalation study (dose linearity and range finding)
  • Tissue distribution study ( brain, heart, liver, lung and kidney)
  • Site specific absorption studies via intra-duodenal dosing
  • Bile collection and analysis for biliary excretion studies

PK-PD Evaluation

A correlation can be established using data from PK and pharmacology studies

Allometric scaling

Allometric scaling can be perform for predition of human pharmacokinetics for any test compound using PK data from mouse, rat and dog.

DMPK Services

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