Oral Absorption Principles Flashcards
What is the F of IV drugs?
100%
What is F?
bioavailability
-indicates the % of the original dose that is available to the systemic circulation
What is the F of oral dosage forms?
always <1
What is absorption?
process by which unchanged drug is released from dosage form (disintegration/dissolution) and proceeds from administration site into systemic circulation
What are the steps in the absorption process?
disintegration
dissolution
drug in solution
permeation
absorbed drug
Differentiate between dissolution and permeation.
dissolution:
-all drugs must dissolve in the aqueous environment of the administration site for absorption to occur
permeation:
-all drugs must permeate across the lipid barriers
What are the rate-limiting steps of absorption?
disintegration: almost never rate-limiting
dissolution:
-the slow step in absorption is the rate at which the drug dissolves in aqueous solution
permeation:
-the slow step in absorption is the rate at which the dissolved drug moves across the polarized epithelium of the GIT
How can dissolution be enhanced?
taking drug with full glass of water or high fat meal
How can permeation be enhanced?
requires biopharmaceutical factors
What are the primary PK parameters of absorption?
Ka: rate of absorption
F: extent of absorption
What are the descriptive PK parameters of absorption?
AUC: extent of absorption
Cmax: extent and rate of absorption
Tmax: rate of absorption
What reduces the extent of absorption?
first-pass effects
What are the factors that influence systemic drug absorption?
anatomical/physiological functions at absorption site
-nature of membrane
-anatomic considerations
-perfusion
-pH
physiochemical properties of the drug
-solubility
-partition coefficient
nature of drug product and dose size
How does the nature of the membrane impact oral absorption?
properties of membrane
-permeability (lipid soluble, unionized, unbound drug can cross)
-low surface tension due to proteins (allows drug to have access to membrane)
-electrical properties due to differential distribution of ions (allows for an electrochemical gradient)
functional, anatomical barrier
-polarized epithelia (allow for vectoral transport)
Why are anatomic considerations important in oral absorption?
absorption varies in different areas of the GIT
What is the primary site of absorption? What are some reasons it is the primary site of absorption?
small intestine
-large surface area (villi, microvilli)
-high blood perfusion rate; best permeability characteristics
What is the importance of motility in absorption?
creates an absorption window
gastric emptying influences rate and maybe extent of absorption
intestinal motility determines residence time at absorption site (extent)
What are some factors which can impact motility?
drugs
food
disease
Describe the impact of GIT secretions on absorption.
mucus:
-drug must solubilize in mucus to access epithelial cells for transport (impacts rate and extent)
bile:
-can help solubilize lipid soluble drugs
enzymes:
-can breakdown drug (1st pass effect)
ions:
-can complex with drugs and prevent absorption
What is the impact of varying fluid volumes throughout the GIT on absorption?
different volumes in different sections of the GIT leads to different concentration gradients throughout the GIT
What is the impact of presystemic metabolism and transporters on absorption?
affects the bioavailability of some drugs (reduces)
-interaction with hepatic/gut wall enzymes
-some drugs are substrates for uptake/efflux
What is the impact of blood perfusion on absorption?
establishes the concentration gradient across GIT
-decreased perfusion=decreased rate of absorption
What happens to P x SA as you transition from the small intestine to the large intestine?
P x SA reduces
-no villi
-large intestine has lower permeability and SA
Which formulation is particularly impacted by the reduced P x SA of the large intestine?
controlled release
What are the physicochemical factors affecting absorption?
size (small>large)
solubility in aqueous solution
-hydrophilic drug dissolves in aqueous solution
-ionized drug is more rapidly dissolved
ionization (unionized can permeate)
protein binding (unbound can permeate)
partition coefficient (K)
-measure of lipophilicity (more lipophilicity can enhance permeation)
How does nature of drug product and dose impact absorption?
biopharmaceutics:
-dissolution rate and extent is an important determinant of absorption rate and extent
size of dose:
-large the dose, lower the extent of absorption (less volume to solubilize into)
