This screening assay is used to determine the bioavailability/exposure of test compounds after two routes of administration to female rabbits.
Required from Customer
- Test compound in powder form or preformulated
- Dose routes—intravenous bolus (IV) and oral gavage (OG)
- Dose (mg/kg) of test compound
- Molecular mass (exact mass) of each test compound and its salt form
- MSDS or handling and storage information, e.g., light sensitive, store at -20°C, etc.
- If applicable, instructions for dose vehicle preparation
- In-life observations on each rat
- A table containing test compound concentrations 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 and Tmax for each compound, and half life, clearance, and volume of distribution of each compound after IV administration, if applicable
- Test compound in an appropriate dosing vehicle
- Conscious, fasted, female New Zealand White rabbits weighing between 3.0 and 5.0 kg; water is offered ad libitum
- Three rabbits (N=3) per dose route
- Sample blood from an auricular vessel (vein or artery) at the following time points:
Typically predose, 5 (IV), 15, 30 min, 1, 3, and 6 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 6 point calibration curve*
- Non-compartmental analysis is used to determine PK parameters for each test compound
- At least 60% 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.
- 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:
• any two dose routes—IV, OG, IP, or SC
• the dose (mg/kg) of each dose route
• the formulation instructions, if applicable
- The customer can request:
• 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