Drug Absorption #3 Flashcards
pH partition theory is related to
absorption
What is the assumption of the pH partition theory
the membrane that molecule would have to cross are lipid and because of that the unionized form is more lipid soluble–> leading to it being absorbed
Acidic drugs would be most unionized in the ____, while basic drugs would be better absorbed in the ______
stomach; intestine
_______ form are not absorbed
ionized
T/F The Surface area of the intestine WAS taken into consideration for the pH partition theory
FALSE: WAS NOT
T/F For a drug undergoing passive diffusion, movement of drug across the membrane stops when drug concentration on both sides of the membrane becomes equal
FALSE
o Drug movement across the membrane does not stop when the concentration is equal on both sides
o No net gain or loss of drug on either side of the membrane
o The drug is at equilibrium
o Movement in both directions is equal
Passive diffusion is driven by ______
kinetic energy
Which of the following would decrease when a drug is more rapidly absorbed?
a) AUC
b) Efficacy
c) Cmax
d) Potency
e) Tmax
e) Tmax
The relationship between _____, _____, and _____ are directly related
- partition coefficient
- lipid solubility
- rate of absorption
The absorption rate ______ as the lipid solubility is increasing
increases
Lipophilic groups have better absorption, what mechanism do they use?
passive diffusion
Hydrophilic groups all essentially have the same absorption, what mechanism do they use?
carrier mediated or paracellular
T/F There are fewer pores/channels in the ileum compared the jejunum so absorption is lower
TRUE
An experiment that would allow us to distinguish between carrier mediated vs. diffusion. (3)
an experiment that depends on
- energy
- inhibits the carrier
- saturation occurs
Prodrugs are _______–>_____-
inactive, the body changes the prodrug to its active form
What are the reasons as to why prodrugs are developed? (6)
- poor absorption
- poor solubility
- instability
- poor distribution
- poor taste
- pain on injection
Weak Acids have…
a higher absorption at lower pH (more unionized form)
Absorption of ____ is very slow
ions
The addition of an -O functional group makes the drug more _____ soluble–>
lipid ; has a higher absorption
The rate of ____ can effect the amount of drug that is actually absorbed
dissolution
The AUC for large particles is typically smaller…why?
b/c the drug must first go into solution–> large particles take longer to go into solution
T/F A drug administered as an oral solution would be expected to be completely absorbed from the GI tract
FALSE
- Could precipitate in stomach/intestine
- Decomposition could occur in stomach/intestine
- First-pass metabolism
- If transporter required, saturation and/or competition is possible
T/ F Polar drugs would primarily be absorbed from the SI by transcellular route
FALSE
- generally move by paracellular transport
- polar compounds would not easily cross through lipophilic membrane
dissolution
a process; how solid gets turned into a solution
Particle size effects _____ and _____
dissolution and absorption
_____ is more water soluble
ionized
more ionized form
Acid dissolve more at _____ pH
Base dissolve more at ____ pH
higher; lower
Ketoconazole is a weak ______. Which means that it is less soluble at a higher pH
base
Why is the salt form of a drug usually administered?
because the salt form is more soluble
Salt form vs. Free Form
Faster RATE and EXTENT of absorption in the salt form (shorter Tmax and higher AUC)
T/F pH of the environment HAS an effect on the dissolution rate of the salt form
FALSE: DOES NOT HAVE
______ change pH in microenvironment around dissolving particle
excipients
polymorphism
the ability of a molecule to exist in more than one crystalline state
T/F Only one form of the polymorphic state is stable
TRUE; overtime the unstable will convert to the stable form (beta form)
metastable form
if conversion rate is SLOW
Which form has the greatest solubility?
Stable or Unstable
Unstable (smaller AUC)
Do we always want RAPID dissolution?
NO. Not for drugs that are extended release, blood pressure or glucose medications
What would be the expected rate limiting step in the absorption process for a solid poorly soluble and highly permeable drug?
a) dissolution
b) diffusion
c) blood flow
dissolution
amorphous state (2)
- molecules are arranged in the solid form RANDOMLY
- higher solubility–> higher absorption
crystalline state
-molecules are arranged in a more STRUCTURED form
The bioavailability of various drug products can be evaluated by comparing their plasma conc.-time curves. The 3 most important parameters of comparison obtained directly from the curves are
A. biologic half life, absorption rate constant, AUC
B. Time of peak concentration (tmax), absorption rate constant, elimination rate constant
C. maximum drug concentration, time of peak concentration (tmax), duration of action
D. AUC, time of peak concentration (tmax), maximum drug concentration
E. rate of elimination, AUC, rate of absorption
D. AUC, time of peak concentration (tmax), maximum drug concentration tells us something about RATE and EXTENT of absorption
solvate
the solvent is trapped within the solid crystal
hydrate (2)
- water
- less soluble in water than the anhydrous form
Generally, the greater the degree of solvation the _______ the solubility in a medium that is the same as solvate molecules
LOWER
_____ form is more soluble in water
anhydrous
Ampicillin TriHYDRATE would be ____ solubility than anhydrous form
SLOWER
