ADME-Tox

Physicochemical parameters give information about the “drug-likeness” of the compound, with respect to absorption from the intestine. Information about these properties is also valuable when planning optimum conditions for other in vitro ADME assays.

• Lipophilicity (shake flask method and RP-HPLC screening method)​
• Solubility​
• Stability in plasma, buffer or biorelevant media​
• Plasma protein binding​
• Red blood cell binding​
• Tissue binding​
• Microsome/Hepatocyte binding

Several assays are available for evaluating permeability and identifying drug transporter substrates or inhibitors.

• PAMPA (parallel artificial membrane permeability assay)​
• Caco-2/MDCK permeability​
• Efflux transporters​
• Uptake transporters

High-quality in vitro metabolism services are available to evaluate the metabolic fate of the compound in liver or extrahepatic tissues. The samples are analysed with state-of-the-art UPLC/HR-MS equipment.

• Metabolic stability​
• Metabolite identification and profiling​
• Metabolite synthesis​
• Identification of metabolising enzymes​
• Non-CYP mediated metabolism​
• Extrahepatic metabolism​
• Metabolite production and NMR identification​
• Reactive metabolite screening​
• Acyl-Glucuronide reactivity​
• IVIVE & PBPK modelling​

Evaluating drug-drug interaction risk is a crucial part of drug safety evaluation required by the drug regulatory authorities. The available services cover the identification of metabolising enzymes, enzyme inhibition and enzyme induction assays, as well as transporter-mediated drug-drug interactions.

• CYP inhibition​
• UGT inhibition​
• Inhibition towards other metabolising enzymes​
• CYP induction​
• UGT induction​
• Transporter interactions

Information about in vitro toxicity early on during the drug discovery process support your internal decision making. The available non-GLP in vitro toxicology assays are planned for cost-efficient screening with low compound consumption and cover the most commonly faced toxicity related challenges.

• Cardiotoxicity screening​
• hERG Predictor fluorescence polarisation assay​
• Electrophysiology (via our partner Axxam)​
• Genotoxicity screening​
• Cytotoxicity screening​
• Mechanistic toxicity assays​
• Hematologic toxicity

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• The in vivo DMPK services cover a variety of animal experiments in several species. In-house rodent PK studies are carried out in AAALAC accredited animal facilities and studies with other species are completed together with selected European in-life partners.​
• Animal pharmacokinetics​
• In vivo MetID​

Safety metabolism studies help you to confirm that the exposure to human metabolites is adequate in preclinical safety species, or to effectively identify potential MIST (metabolites in safety testing) issues in time, through a battery of different types of in vivoMetID studies.

• Metabolite profiling and characterisation in pre-clinical species​
• Human metabolite profiling and characterisation (FIM, SAD, MAD)​
• Human MIST analysis (MAD + preclinical safety species)​
• Metabolite profiling and characterisation in radiolabelled human ADME study​
• Metabolite profiling in milk secretion studies