Overview of Services
The Exploratory Pharmacology Core focuses on analyzing the ADME (absorption, distribution, metabolism, and excretion) and pharmacokinetic properties of novel chemical probes and potential new drugs.
In addition to determining the efficacy and selectivity of the compound, knowing these properties allow scientists to effectively select compounds for further development and optimization, thus advancing discovery in biology and chemistry.
In Vitro Analysis
- Aqueous Solubility: Compound stability in an aqueous solution is measured using an automated kinetic solubility method. The concentration of the compound in a saturated pH-buffered aqueous solution is determined by UV absorbance (250-498 nm) and compared to the spectra of a precipitation-free reference solution.
- Cellular/BBB Permeability: Compound permeability is measured using an automated high-throughput, non-cell based, parallel artificial membrane permeability assay (PAMPA). The assay can be modified to predict trans-cellular intestinal absorption (gut permeability) or blood-brain-barrier diffusions (CNS penetration).
- PAMPA-based Excipient Screening: A quick, cost-effective, and reasonably accurate method, suitable for use in preclinical development, to assess the effect of excipients on the permeability of sparingly soluble drug candidates, and guide formulation efforts for use of the compound in vivo.
- CYP450 Inhibition Profiling: Compounds that inhibit P450s may cause the toxic accumulation of other substrates. Evaluation of the test compounds as inhibitors of selected human CYP450s (1A2, 2C9, 2D6, 3A4) is performed using isoenzyme specific P450-Glo™ assay kits (Promega).
- Hepatic Microsome Stability: Metabolic stability of compounds is determined at a single concentration using species specific liver microsomes that contain many drug-metabolizing enzymes (including cytochrome P450s (CYPs), flavin monooxygenases, carboxylesterases, uridine glucuronide transferase and epoxide hydrolase). S9 fractions may be substituted for microsomes to assess the effects of additional metabolizing enzymes (aldehyde oxidase, glutathione transferase, monoamine oxidase, and sufurotransferase) on compounds metabolism.
- Plasma Protein Binding: The percentage of compound bound to plasma proteins is determined by rapid equilibrium dialysis and quantified by LC/MS/MS.
- Plasma Stability: The stability of a compound in plasma is measured by LC/MS/MS.
- Cytotoxicity: The potential toxic effects of compounds on cells are determined using a homogeneous, luminescence assay that measures the number of dead cells in culture using V79MZ cells (low metabolic activity) and primary or immortalized human hepatocytes (high metabolic activity).
In Vivo Drug Metabolism and Pharmacokinetic Assays
- Rapid Assessment of Compound Exposure: This experiment is a rapid and efficient compressed in vivo PK screening method used to determine an estimated in vivo exposure (AUC) of novel chemical probes. RACE can be used for dose finding studies, the assessment of formulations, and tissue distribution.
- Comprehensive Pharmacokinetic Analysis: Compounds that show promising in vitro drug like properties, or that are more advanced are subjected to a comprehensive pharmacokinetic analysis. Standard pharmacokinetic parameters including Cmax T1/2, bioavailability (%F), and AUC are determined.
- Bioanalytical Method Development and Sample Analysis: Bioanalytical method development and sample analysis provides quantitative measurement of an active drug and/or its metabolites in biological matrices (plasma, brain tissue, urine etc.). Utilizing state-of-the-art LC/MS/MS and HPLC instrumentation, bioanalytical methods are developed and optimized for sensitivity, recovery, and reproducability to provide our clients with accurate, high quality bioanalytical data.
- Results Reporting: A number of different reporting options are available from summary data to full written reports.
1) If you are a new user to the core:
2) If you are an existing user to the core:
- Please log into iLab at the top right of the page.
- Go to the "Request Services" tab to initiate a project request.
- Fill out the form after pressing the "request service" button.
- Submit the project request to the core.
If you do not have an iLab account, please click the "sign up" link on the top right to create an account
Layton Smith PhD | Director
Location and hours of operation
Monday through Friday
8AM to 5PM
Lake Nona, FL