This assay is used to determine the bioavailability / exposure of test compounds in male dogs after two routes of administration.
Required from Customer
- Test compound in powder form or preformulated
- Dose routes—two dose routes: intravenous bolus (IV) and/or orally (PO)
- Dose (mg/kg) of test compound
- Molecular mass (exact mass) of the test compound and its salt form
- MSDS or handling and storage information, e.g., light sensitive, store at -20°C, stability, solubility, purity, and activity
- If applicable, instruction for dosing vehicle preparation
- In-life observations on each dog
- A table containing test compound concentration in plasma samples at each time point
- A table listing relative exposure (bioavailability) based on the AUC for each compound and Concentration vs. Time profiles
- A table containing appropriate pharmacokinetic parameters for each dose route: Cmax, Tmax, half life, clearance, and volume of distribution after IV and PO administration as applicable
- Test compound in an appropriate dosing vehicle suitable for intravenous and/or oral gavage dosing
- Conscious, fasted, male Beagle dogs weighing between 8 and 17 kilograms; water is offered ad libitum
- Two (2) leg crossover:
- Three dogs (N=3) per dosing route per test compound per leg
- Up to one (1) week washout period between legs
- Sample blood from the cephalic vein at the following time points (9 IV and 8 PO points):
- Typically predose, 5 (IV), 15, 30 min, 1, 2, 4, 8, and 24 hours
- Prepare plasma from each sample and freeze
- Determine the concentrations of test compounds in dosing solution and incurred samples using a generic LC-MS/MS method with a minimum 8 point calibration curve*
- Non-compartmental analysis is used to determine PK parameters for each test compound
- 5/8 of the calibration standards must be within ±20% of the theoretical values to accept the analytical run
- The results from this study are provided to the customer in the ExpressPlus report format, which may include graphical representations of data and comparison with historical data for reference compounds.
- *The analytical rigor does not include a pre-study validation, and QCs will not be used for sample analysis.
- The amount of test compound or formulation that is required depends upon the dose, i.e., mg test compound per kg of body weight, and the number of dogs.
- If required, Absorption Systems can determine a suitable dosing vehicle and prepare it for the experiment. Alternatively, Absorption Systems can prepare the dosing vehicle if the customer provides instructions.
- One hour formulation prep cost has been included in the study price. Additional time required for formulation preparation will be charged.
- Dose vehicle development is not included as part of this assay.
- The standard anticoagulant is sodium heparin. The customer can specify that another anticoagulant be used.
- The customer must specify:
• the dose routes—IV and/or PO
• the dose (mg/kg) of each dose route
• the formulation instructions, if applicable
- The customer can request for an additional fee:
• the number of replicates (typically 3)
• different time points and an extended duration
• that Absorption Systems determine a suitable dosing vehicle
• that Absorption Systems prepare the dosing vehicle using the customer’s instructions