Bioavailability dependant on several things:
- Route of administration
- The drug’s ability to cross membranes
- The drug’s binding to plasma proteins and intracellular component
- Membranes separate the body in components
- The ability of membranes to act as barriers is related to its structure
- Lipid Soluable compounds (many drugs) pass through by becoming dissolved in the lipid bylayer.
- Glucose, H20, electrolytes can’t pass on their own. They use pores.
- In excitable tissues, the pores open and close.
- Movement occurs by:
- passive diffusion
- active transport
- facilitated diffusion
Passive Diffusion Review:
- No energy expended.
- Weak acids and bases need to be in non-ionized form (no net charge).
- Drugs can also move between cell junctions. BBB is exception.
- Must be lipid soluable to pass through pores.
- Osmosis is a special case of diffusion
- A drug dissolved in H2O will move with the water by “bulk flow”
- Usually limited to movement through gap junctions because size too large for pores.
Active Transport Review:
- Requires energy and requires a transport protein
- Drugs must be similar to some endogenous substance.
- Can carry substances against a gradient
- Some drugs may exert their effect by increasing or decreasing transport proteins.
Facilitated Diffusion Review:
- Requires transport protein
- Does not require energy
- Very few drugs move this way
- Drug gets engulfed by cell via invagination
- Very few drugs move this way and only in certain cells.
Regulation of distribution determined by:
- Lipid permeability
- Blood flow
- Binding to plasma proteins
- Binding to subcellular components
Volume of Distribution (Vd) – is a calculation of where the drug is distributed.
Vd = amount of drug given (mg)
concentration in plasma (mg/ml)
Calculate the Vd and compare to the total amount of body H20 in a person.
-if Vd = total amount of body (approx. 42) is uniformly distributed
-if Vd is less than 42 – retained in plasma and probably bound to plasma proteins
-if Vd is more than 42 – concentrated in tissues
This is not a “real value” but tells you where the drug is being distributed.
Placental Transfer of Drugs
- Some drugs cause congenital anomalies
- Cross placenta by simple diffusion
- Must be polar or lipid-insoluable Not to Enter
- Must assume the fetus is subjected to all drugs taken by the mother to some extent.