Oral Absorption Principles

Question 1

What is the F of IV drugs?

Answer 1

100%

Question 2

What is F?

Answer 2

bioavailability
-indicates the % of the original dose that is available to the systemic circulation

Question 3

What is the F of oral dosage forms?

Answer 3

always <1

Question 4

What is absorption?

Answer 4

process by which unchanged drug is released from dosage form (disintegration/dissolution) and proceeds from administration site into systemic circulation

Question 5

What are the steps in the absorption process?

Answer 5

disintegration
dissolution
drug in solution
permeation
absorbed drug

Question 6

Differentiate between dissolution and permeation.

Answer 6

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

Question 7

What are the rate-limiting steps of absorption?

Answer 7

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

Question 8

How can dissolution be enhanced?

Answer 8

taking drug with full glass of water or high fat meal

Question 9

How can permeation be enhanced?

Answer 9

requires biopharmaceutical factors

Question 10

What are the primary PK parameters of absorption?

Answer 10

Ka: rate of absorption
F: extent of absorption

Question 11

What are the descriptive PK parameters of absorption?

Answer 11

AUC: extent of absorption
Cmax: extent and rate of absorption
Tmax: rate of absorption

Question 12

What reduces the extent of absorption?

Answer 12

first-pass effects

Question 13

What are the factors that influence systemic drug absorption?

Answer 13

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

Question 14

How does the nature of the membrane impact oral absorption?

Answer 14

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)

Question 15

Why are anatomic considerations important in oral absorption?

Answer 15

absorption varies in different areas of the GIT

Question 16

What is the primary site of absorption? What are some reasons it is the primary site of absorption?

Answer 16

small intestine
-large surface area (villi, microvilli)
-high blood perfusion rate; best permeability characteristics

Question 17

What is the importance of motility in absorption?

Answer 17

creates an absorption window
gastric emptying influences rate and maybe extent of absorption
intestinal motility determines residence time at absorption site (extent)

Question 18

What are some factors which can impact motility?

Answer 18

drugs
food
disease

Question 19

Describe the impact of GIT secretions on absorption.

Answer 19

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

Question 20

What is the impact of varying fluid volumes throughout the GIT on absorption?

Answer 20

different volumes in different sections of the GIT leads to different concentration gradients throughout the GIT

Question 21

What is the impact of presystemic metabolism and transporters on absorption?

Answer 21

affects the bioavailability of some drugs (reduces)
-interaction with hepatic/gut wall enzymes
-some drugs are substrates for uptake/efflux

Question 22

What is the impact of blood perfusion on absorption?

Answer 22

establishes the concentration gradient across GIT
-decreased perfusion=decreased rate of absorption

Question 23

What happens to P x SA as you transition from the small intestine to the large intestine?

Answer 23

P x SA reduces
-no villi
-large intestine has lower permeability and SA

Question 24

Which formulation is particularly impacted by the reduced P x SA of the large intestine?

Answer 24

controlled release

Question 25

What are the physicochemical factors affecting absorption?

Answer 25

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)

Question 26

How does nature of drug product and dose impact absorption?

Answer 26

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)