Perfusion studies are often performed when compounds are being narrowed down to the final candidates. These models can be used to rank order compounds against one another, to benchmark a new drug against an already marketed drug that is being used for a similar indication, to optimize formulations or to assess interactions with transporters. The utility of these models is their flexibility to be manipulated as you would the conditions for a pharmacokinetic study. Since we are working with actual organs, they are often able to tolerate a harsher environment that cannot be achieved in more delicate in vitro systems.
Kinetics of Drug Elimination
Simplified with Exemplary Service
Rats are anesthetized and a specific segment of intestine is isolated through insertion of cannulae (pre- and post-segment). Buffer containing test compound is perfused through the segment, and aliquots of perfusate buffer are collected at various time points/intervals in order to calculative effective permeability into the intestinal mucosa. Plasma samples can also be taken in parallel to assess pharmacokinetics.
Rats are anesthetized, and the left carotid artery is cannulated. Buffer containing test compound is perfused through the carotid artery into the brain for a designated period of time. Perfusion is immediately stopped and the brain is collected from each animal in order to calculate permeability into the brain itself.
The liver is isolated from a rat, and is placed into a special perfusion chamber. The portal and hepatic veins are cannulated, and buffer containing test compound is perfused through the liver. Aliquots of perfusate buffer are collected at various time points/intervals in order to calculate effective permeability into the liver. The bile duct can be cannulated as well in order to determine how much of the compound is undergoing biliary secretion.
EA803 In Situ Rat Brain Perfusion
EA814 Rat Closed Loop Intestinal Perfusion
EA815 Rat Single Pass Intestinal Perfusion
EA816 Rat Recirculating Intestinal Perfusion
EA150 Stability in Gastric Fluids
EA151 Stability in Plasma
EA201 Express Unidirectional Caco-2
EA202 Express Bidirectional Caco-2
EA203 Express MDR1-MDCK P-gp Interaction
EA204 Express MDR1-MDCK P-gp Inhibition
EA205 Unidirectional Permeability though Intestinal Tissue
EA206 Bidirectional Permeability through Intestinal Tissue
EA401 Express Metabolic Stability in Human Liver Microsomes
EA402 Express Metabolic Stability in Rat Liver Microsomes
EA403 Metabolic Stability Liver Microsomes
EA802 Test Compound Brain to Plasma Ratio in Rat
EA813 Express ABT PK in Rats
Van Deusen J. et al., Use of a physiologically based pharmacokinetic model to study the time to reach brain equilibrium: an experimental analysis of the role of blood-brain barrier permeability, plasma protein binding, and brain tissue binding. J Pharmacol Exp Ther. 2005 Jun; 313(3):1254-62.
What are the different models of intestinal perfusion?
We offer three models: Closed loop, single pass with perfusate and or plasma collection, and recirculating.
How long does a typical intestinal perfusion run?
This is dependent on which intestinal perfusion model is chosen. A closed loop model can have up to 4 time points up to 2 hours. Whereas single pass and recirculating is up to 90 minutes with 6 timepoints/intervals.
Can you only monitor for disappearance in intestinal perfusion?
We monitor both the disappearance of the drug which is from the perfusate and are able to monitor appearance in the blood.
How can you make the brain perfusion model more physiologically relevant?
This model can be made more representing by altering the perfusion buffer, the addition of protein, as well as the addition of transporter inhibitors.
Which important agents are used in determining tissue viability in a liver perfused model?
The most important agents in determining tissue viability are the perfusate composition and O2-carrying capacity.
We have optimized our perfusion models to generate data that can accurately predict in vivo outcomes.
Our scientists have extensive experience and refined skills in handling these tissues to ensure their physiological integrity is retained.
Our capabilities are broad and extend to not only cold compounds but radiolabeled compounds as well.