With a team of experienced scientists and ADME experts, we offer a comprehensive suite of services tailored to your specific drug development needs. Our expertise encompasses:
In vitro metabolic stability studies are conducted to measure the rate of disappearance of the test article in liver microsomes, S9 fraction, or hepatocytes. The in vitro data are valuable in predicting the in vivo clearance and estimating bioavailability. We offer a variety of metabolic stability assays with customizable assay conditions:
• Hepatocyte Stability: Hepatocytes contain the all hepatic drug metabolizing enzymes (phase I and phase II) and cofactors within the intact cells. It is a preferred system for in vitro drug metabolism studies.
• Microsomal Stability: Liver microsomes are subcellular fractions which contain all active CYP450 enzymes that are responsible for the metabolism of most drugs. Microsomes are easy to store and use enabling, cost-efficient in vitro drug metabolism studies.
• S9 Stability: The S9 fraction consists of microsomes and cytosol, which contains a wide variety of both phase I and phase II enzymes.
• Plasma Stability: Blood contain esterase and protease activities. Compounds with ester and amide bonds should be routinely tested for plasma stability.
• Metabolite Identification: Stability study can be extended to identify the metabolites supported by our high resolution mass spectrometry.
• Kinetic Solubility: The solubility of a compound is an important parameter in predicting its absorption from the gastrointestinal tract. In addition poor solubility can also impact the quality of data in other assays. Kinetic solubility requires a relatively small amount of compound, especially useful in the early discovery phases.
• LogD: The distribution coefficient is the concentration ratio of the compound in a lipophilic phase such as octanol and a hydrophilic phase like water. LogD is an important parameter in predicting many ADME properties such as solubility in gut, cellular permeability and the ability to penetrate the blood-brain barrier. We provide a logD service using shake flask method in octanol/buffer.
The binding of a drug to plasma proteins is critical to understanding the pharmacokinetics of the drug. In general, only the free (unbound) drug is available for diffusion to extravascular or tissue sites where therapeutic effects occur. Services include:
• Plasma Protein Binding: We provide a plasma protein binding service using rapid equilibrium dialysis to determine free drug concentration (fraction unbound) in plasma for a range of species.
• Microsomal Protein Binding
• Blood Partitioning: Service to determine the concentration of the drug in whole blood compared to plasma (blood to plasma ratio).
Cytochrome P450 (CYP) Inhibition
Help o understand the potential drug-drug interaction liabilities of your compounds by using our cytochrome P450 (CYP450) reversible inhibition assay for a range of isoforms. Services include:
• CYP inhibition (IC50): Determine test compound concentration which produces 50% inhibition using probe substrates for a range of isoforms
• Time Dependent Inhibition (IC50 Shift): Determines the IC50 with a pre-incubation in presence of NADPH and without pre-incubation.
• Determine which CYP enzyme(s) are involved in metabolism using human liver microsomes or recombinant enzymes. Services include:
Permeability and Transporter Assays
SR tests drug permeability and interaction with transporters to provide key insight into the ability of drug molecules to across biological membranes and the potential for drug interaction with transporters. Tests include:
• Caco-2 Permeability
• MDCK Permeability
• Transporter Assays
• Microsomes, S9, hepatocytes or ex vivo samples
• Initial screening assessments or more definitive determinations using high resolution mass spectrometry