Distribution Equations and Related Applications Flashcards
(31 cards)
Define drug distribution:
The reversible transfer of drug from one site to another within the body.
What is drug distribution?
The reversible transfer of drug from one site to another within the body.
Via what pathways can molecules (drugs) cross cell membranes?
Paracellular - Move via the gaps between cells
Transcellular - Move through the cells by simple or facilitated mechanisms
What are the major constraints of transmembrane passage in order of most to least important?
- Molecular weight
- P (LogP) value
- Charge
What does the pH-partition hypothesis state?
Once the un-ionised quantity of a drug on both sides of the membrane is equal, the net flow of the drug will become zero.
Why is the pH-partition only a hypothesis and not held as true in every situation?
It requires many assumptions, limiting its application. In situations without these assumptions it does not hold up.
What are the two types of cell membrane transporters?
- Equilibrating transporters
- Active/concentrating transporters
What is an efflux pump? What is an influx pump?
Efflux pump: Pumps a given molecule out of cells
Influx pump: Pumps a given molecule into cells
What does the apical side refer to?
The lumen facing side of a cell
What does the basolateral side refer to?
The blood facing side of a cell
State the typical relationship between lipophilicity ad drug transport:
As lipophilicity increases, drug transport improves.
What role do efflux pumps play in the BBB?
They prevent toxic or otherwise dangerous molecules from accumulating in the CSF in order to prevent them from making their way to the brain.
What is the equation for Fbound? What is another notation for Fbound?
Fbound = [drug]bound/[drug]total
Beta
What is the equation for Funbound? What are some other notations for Funbound?
Funbound = [drug]free/[drug]total
Ffree, alpha
What is the equation for free/unbound drug concentration?
Free = Ctotal*Fu
Why is drug-protein binding essential to our understanding of drug distribution?
When drugs bind to proteins they are too large to diffuse efficiently.
Only the free/unbound portions of the drug can distribute.
If a tissue is in equilibrium with the plasma what equation holds true?
Cunbound,tissue = Cunbound,plasma
What two processes describe a drug’s affinity for tissue distribution?
- Protein binding
- Partitioning
What is the partition coefficient equation for distribution?
Ptissue/blood = Cdrug,tissue/Cdrug,plasma
State the equation used to identify the percentage of a drug in plasma:
(Vp/V)*100 = %Plasma
State the equation used to identify the percentage of a drug in tissue:
(Vt/V)*100 = %Tissue
What is the tissue distribution half life equation? State all variations.
t1/2 = ln(2)/Kt = (ln(2)*P)/(Q/Vt)
State all variations of the tissue distribution half life equation:
t1/2 = ln(2)/Kt = (ln(2)*P)/(Q/Vt)
