DMPK & ADME-Tox

To achieve success in drug discovery, it is essential to possess a thorough comprehension of the biological context, combined with expertise in the property space necessary to produce safe and effective drugs. DMPK plays a crucial role in this success, as the primary reasons for drug attrition – clinical efficacy and safety – are closely associated with exposure in critical tissues, either on-target or off-target.

LAXAI provides an extensive and adaptable selection of in vivo and in vitro DMPK/ADME studies that cover a broad range of activities from hit-to-lead and lead optimization phases to candidate selection.

DMPK (Drug Metabolism and Pharmacokinetics) focuses on the study of how drugs are metabolized and distributed in the body, and how they affect the body’s systems. This includes the study of drug absorption, distribution, metabolism, and excretion (ADME). DMPK is critical in drug discovery and development because it helps researchers to understand how drugs will behave in-vivo or in the human body. This understanding can help to optimize drug design and dosing regimens, and to identify potential safety concerns.

ADME-Tox (Absorption, Distribution, Metabolism, Excretion, and Toxicity) includes the study of not only the pharmacokinetics of drugs but also their toxicity in biological systems. ADME-Tox studies how drugs are absorbed, distributed, metabolized, and excreted as well as their potential to cause adverse effects. This field helps to ensure that drug candidates are safe and effective for use.

Highlights:

  • In-vitro and In-vivo studies executed with best in industry turnaround times.
  • Sciex 4500 QTrap is equipped with LightSight software, which is exclusively useful for metabolite identification studies.
  • Expert’s data-driven scientific interpretations to drive customer programs.
  • Enhancing the arms in SAR modifications in integrated drug discovery programs.

Capabilities:

  • Physicochemical Screening: Solubility studies by Kinetic Method, Themodynamic method in biorelevnat media (FaSGF, FaSSIF, FeSSIF) and in PBS, Stability studies in fresh plasma, in fresh blood, in biorelevant media (FaSGF, FaSSIF, FeSSIF) and Chemical stability (across pH)
  • Permeability Assays: PAMPA, Caco-2, MDCK-MDR1
  • Metabolism: Metabolic Stability in Liver microsome (mice, rat, dog, monkey, human), Hepatocytes (mice, rat, dog, monkey, human), Liver S9 fractions (mice, rat, dog, monkey, human), Met-ID in vitro and in vivo, CYP inhibition (two-point or IC50 determination), Time dependent CYP inhibition, CYP Induction & CYP profiling and GSH Trapping
  • Distribution: Protein binding (equilibrium dialysis), Tissue distribution in rodents (using cold compound), Assessment of blood-to-plasma ratio
  • Excretion: In rodents using metabolic cages with cold compound, Biliary excretion in rats
  • Pharmacokinetics: PK in Mice (Balb/C, SAM, C57BL/6, nude), Rats (Sprague Dawley and Wistar), Beagle dogs, Rabbits (New Zealand white), Hamsters (Golden Syrian) & Monkeys, Dose escalation studies(rodents, rabbits, hamsters, dogs), Repeat dose PK study (rodents, rabbits, hamsters, dogs), Cassette dosing/Snap-shot PK, CSF collection in rats/dogs

Infrastructure and Instrumentation:

  • LC-MS/MS 8045 with UPLC (Shimadzu)
  • LC-MS/MS 4500 QTrap with UPLC (Sciex)
  • HPLC-1 : Prominence iSeries (Shimadzu)
  • HPLC-2 : Prominence iSeries (Shimadzu)
  • Thermo Mixer (Eppendorf)
  • Turbo Vap evaporator (Biotage)
  • Positive pressure 96 SPE assembly (Biotage)
  • Refrigerator (Samsung)
  • Tissue homogenizer (IKA)
  • HT Dialyser (HT Dialysis LLC)
  • Vacuum kit for solubility (Millipore-Merck)
  • Microplate shaker (VWR)
  • Shaking water bath : temperature controlled (Julabo)
  • -80°C Deep freezer (Eppendorf)
  • -20°C Deep freezer (Samsung)
  • Centrifuge (Eppendorf)
  • Micro plate shaker (VWR)
  • CO2 incubator (Eppendorf)
  • pH meter (Eutech)
  • Vortex mixer (Spinix)
  • Microcentrifuge (Spinwin)
  • Sonicator (Athena)
  • Biosafety cabinet (Fresh air flow system)
  • -20°C Deep freezer (Samsung)
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