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

Deliverables

• 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: C_max, T_max, half life, clearance, and volume of distribution after IV and PO administration as applicable

Substrate

• Test compound in an appropriate dosing vehicle suitable for intravenous and/or oral gavage dosing

Assay System

• Conscious, fasted, male Beagle dogs weighing between 8 and 17 kilograms;  water is offered ad libitum

Assay Conditions

• 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

Assay QC

• 5/8 of the calibration standards must be within ±20% of the theoretical values to accept the analytical run

Notes

1. 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.
2. *The analytical rigor does not include a pre-study validation, and QCs will not be used for sample analysis.
3. 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.
4. 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.
5. One hour formulation prep cost has been included in the study price. Additional time required for formulation preparation will be charged.
6. Dose vehicle development is not included as part of this assay.
7. The standard anticoagulant is sodium heparin. The customer can specify that another anticoagulant be used.

Options

1. The customer must specify:
   • the dose routes—IV and/or PO
   • the dose (mg/kg) of each dose route
   • the formulation instructions, if applicable
2. 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