Lecture 3 1/25/24

Question 1

Which factors must be considered when deciding on an extravascular route of administration?

Answer 1

-rate of absorption
-extent of absorption
-rate of elimination
-clinical factors

Question 2

What are the two most common routes for parenteral extravascular administration?

Answer 2

-IM injection
-SQ injection

Question 3

What are the characteristics of sustained release formulations?

Answer 3

-absorption still occurs during the elimination phase
-absorption occurs at a lesser rate than elimination
-allows for “flip-flop” where absorption regulates how much time the drug stays in the body

Question 4

Which factors impact the stability of drugs in GI fluids during oral administration?

Answer 4

-pH of lumen fluid
-enzymes
-microorganisms

Question 5

Which factors impact the dissolution of drugs in GI fluids during oral administration?

Answer 5

-pH of lumen fluid
-disintegration
-dissolution

Question 6

Which factors impact transport across the membrane during oral administration?

Answer 6

-pH
-presence of food components
-gastric emptying
-intestinal transport time
-surface area
-blood flow

Question 7

Which factors impact the ability to reach systemic circulation during oral administration?

Answer 7

-transport across enterocytes
-metabolism
-P-glycoprotein

Question 8

What is P-glycoprotein?

Answer 8

ATP-dependent efflex pump that pumps foreign substances out of cells

Question 9

How do P-glycoproteins pump in different organs?

Answer 9

-intestine: pump drugs into lumen
-liver: pump drugs into bile duct
-kidney: pump drugs into urinary filtrate

Question 10

What are the characteristics of the hepatic first-pass effect?

Answer 10

-liver can metabolize drugs, significantly reducing the amount of drug available for circulation
-oral doses must often be larger to counteract effect
-the larger the effect (less available for absorption), the more variable the absorption profile between patients

Question 11

How does digestive tract type impact drug absorption?

Answer 11

-monogastrics tend to have increased absorption of oral drugs
-ruminants tend to have less consistent oral absorption

Question 12

Which factors lead to ruminants having less oral absorption?

Answer 12

-large water volume
-microbial degradation of sugars and other compounds
-presence of large amounts of enzymes
-binding to food material

Question 13

Which factors impact transdermal absorption?

Answer 13

-molecule size and lipophilicity
-application site
-skin/membrane thickness
-drug concentration
-surface area
-hydration of skin

Question 14

What is area under the curve used to quantify?

Answer 14

total exposure to a drug

Question 15

What is absolute bioavailability?

Answer 15

-absolute extent of drug absorption into the body
-fraction of administered dose that reaches systemic circulation

Question 16

What is absolute bioavailability a comparison of?

Answer 16

extravascular administration vs. intravenous administration

Question 17

When calculating absolute bioavailability, how is the larger extravascular dose accounted for?

Answer 17

by multiplying the area under the curve fraction by the inverse dose fraction [(AUCex/AUCiv)(Doseiv/Doseex)]

Question 18

What are the potential reasons why absolute bioavailability may be greater than 100%?

Answer 18

-redistribution from other body compartments
-sampling schedule
-“recirculation”
-error

Question 19

What is relative bioavailability a comparison of?

Answer 19

the relative rate and extent of drug absorption between two non-IV drugs

Question 20

What assumption is often made about bioequivalence?

Answer 20

if rate and extent of absorption are similar between the compared drugs, safety and efficacy will also be similar

Question 21

What are the limitations of bioequivalence?

Answer 21

-extra-label use
-drugs with narrow therapeutic index
-compounded products

Question 22

What is the importance of bioequivalence in drug approval?

Answer 22

when applying to produce a generic drug, bioequivalence (similar rate and absorption) must be proven

Question 23

What are the two keys of bioequivalence?

Answer 23

-want a similar rate (Cmax) of absorption
-want a similar extent (area under curve) of absorption