ADME of Therapeutics

ADME of Therapeutics

ADME of Therapeutics (ADMEoT) is the SciLifeLab DDD platform unit for absorption, distribution, metabolism, excretion (ADME), and preclinical profiling.

ADMEoT uses a state of the art laboratory and cutting edge research to help Swedish academic projects in the optimization of hit compound series and deliver lead compounds and candidate drugs of the highest possible quality. We add scientific value to all stages of the preclinical drug discovery and development process.

ADMEoT, as a part of UDOPP (a local platform at the Department of Pharmacy, Uppsala University), is also affiliated with two Innovative Medicines Initiative (IMI) projects: 1) European Gram-negative Anti-bacterial Engine (ENABLE) consortium – as the In Vitro ADME unit; 2) ConcePTION – as a team responsible for bioanalysis of human samples and population PK (popPK) modelling.

SERVICES

Determination and prediction of physico-chemical properties:

• LogP, LogD and pKa determination
• Chemical stability
• Solubility (kinetic and thermodynamic) and its pH dependence

ADME (Absorption, Distribution, Metabolism, Excretion):

• In silico models for prediction of ADME properties
• Plasma protein binding and stability (human and animal plasma)
• Cell-membrane permeability in Caco-2 and MDCK cells
• Active cellular uptake and efflux using cell based assays (identification and characterization)
• Inhibition of active transport (transporter related drug-drug interactions, DDI)
• Metabolic stability in liver microsomes (human an animal)
• Metabolic stability in hepatocytes (human and animal)
• Biotransformation – metabolite profiling and identification
• Metabolic enzyme identification studies (reaction phenotyping)
• Cytochrome P450 inhibition and induction (metabolism related DDI)

Liquid Chromatography-Mass spectrometry (LC-MS):

• Analysis of in vitro ADME samples
• Bioanalysis of animal and human in vivo samples
• Proteomics (targeted and global)

Biopharmaceutics:

• Intact mass determination
• Peptide mapping
• Bioanalysis: mass spectrometry and ligand based assays (LBA)
• Anti-drug antibodies (ADA) characterization: LBA assay
• Protein characterization

Design and evaluation of pharmacokinetic (PK) studies

Physiological-based pharmacokinetics (PBPK) simulations

PK/PD modelling

APPLICATIONS

• Physico-chemical and ADME optimization of the hit and lead compound libraries
• Preclinical characterization of drug candidates
• Drug discovery and development

EQUIPMENT

• Liquid handling robotic system, Hamilton STAR
• Liquid handling robotic system, TECAN Evo
• BSL2 cell culture laboratory with attached equipment
• T3 Sirius instrument for determination of phys-chem properties
• UPLC-MS/MS system Q-Trap 6500 AB Sciex
• UPLC-MS/MS TQ-S micro from Waters
• 2D LC- IM-QToF SYNAPT G2-Si from Waters
• nanoLC/UPLC-Q Exactive HF OrbiTrap from Thermo

DETAILED INFORMATION