Drug distribution Flashcards
What is distribution?
The reversible transfer of drug between the blood and other tissues within the body
What does the rate of distribution depend on?
o Delivery of drug to tissue by perfusion – blood flow
o Permeability of tissue membranes – will differ between tissues etc BBB and capillary in muscle
o Physicochemical properties of the DRUG itself – lipophilic or polar?
o Binding of drug to plasma proteins
Only UNBOUND drug moves across the
membrane
o Binding to acidic phospholipids in tissue membranes
Is tissue perfusion the same across tissues?
NO, e.g. organs receive different blood supplies
When is rapid distribution equilibrium achieved?
In highly perfused tissues (lungs, kidneys, liver, brain)
When is slow distribution equilibrium achieved?
In poorly perfused tissues (skin, adipose, inactive muscle not engaged in physical activity)
What limits perfusion?
Blood flow
What distribution do small lipophilic molecules undergo?
Rapid distibution (fast decline)
What is the time to reach equilibrium and to eliminate drug like for poorly perfused tissues?
Longer than in well perfused organs with large blood supply
What tissue do lipophilic drugs have a high affinity for?
Adipose (low perfusion tissue). This means it takes more time for drugs to distribute and reach max concentration. (Takes time to be eliminated from the adipose - slow distribution and slow elimination)
What is the rate limiting step in permeability limited distribution?
Moving across the membrane (thicker membrane = effective barrier)
What molecules typically experience permeability limited distribution?
Polar hydrophilic molecules, may involve active transporters
What membranes are relatively impermeable?
BBB etc
What effect does drugs binding to plasma proteins have on distribution?
Only UNBOUND molecule passes the membrane, therefore higher plasma binding will decrease distribution
Describe the distribution barrier in the blood brain barrier
Very small pores in the BBB, barrier at capillary level
Describe the distribution barrier in e.g. muscle and kidneys
Capillaries are porous to small molecules, barrier at cellular level
