Lecture 3 1/25/24 Flashcards
Which factors must be considered when deciding on an extravascular route of administration?
-rate of absorption
-extent of absorption
-rate of elimination
-clinical factors
What are the two most common routes for parenteral extravascular administration?
-IM injection
-SQ injection
What are the characteristics of sustained release formulations?
-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
Which factors impact the stability of drugs in GI fluids during oral administration?
-pH of lumen fluid
-enzymes
-microorganisms
Which factors impact the dissolution of drugs in GI fluids during oral administration?
-pH of lumen fluid
-disintegration
-dissolution
Which factors impact transport across the membrane during oral administration?
-pH
-presence of food components
-gastric emptying
-intestinal transport time
-surface area
-blood flow
Which factors impact the ability to reach systemic circulation during oral administration?
-transport across enterocytes
-metabolism
-P-glycoprotein
What is P-glycoprotein?
ATP-dependent efflex pump that pumps foreign substances out of cells
How do P-glycoproteins pump in different organs?
-intestine: pump drugs into lumen
-liver: pump drugs into bile duct
-kidney: pump drugs into urinary filtrate
What are the characteristics of the hepatic first-pass effect?
-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
How does digestive tract type impact drug absorption?
-monogastrics tend to have increased absorption of oral drugs
-ruminants tend to have less consistent oral absorption
Which factors lead to ruminants having less oral absorption?
-large water volume
-microbial degradation of sugars and other compounds
-presence of large amounts of enzymes
-binding to food material
Which factors impact transdermal absorption?
-molecule size and lipophilicity
-application site
-skin/membrane thickness
-drug concentration
-surface area
-hydration of skin
What is area under the curve used to quantify?
total exposure to a drug
What is absolute bioavailability?
-absolute extent of drug absorption into the body
-fraction of administered dose that reaches systemic circulation
What is absolute bioavailability a comparison of?
extravascular administration vs. intravenous administration
When calculating absolute bioavailability, how is the larger extravascular dose accounted for?
by multiplying the area under the curve fraction by the inverse dose fraction [(AUCex/AUCiv)(Doseiv/Doseex)]
What are the potential reasons why absolute bioavailability may be greater than 100%?
-redistribution from other body compartments
-sampling schedule
-“recirculation”
-error
What is relative bioavailability a comparison of?
the relative rate and extent of drug absorption between two non-IV drugs
What assumption is often made about bioequivalence?
if rate and extent of absorption are similar between the compared drugs, safety and efficacy will also be similar
What are the limitations of bioequivalence?
-extra-label use
-drugs with narrow therapeutic index
-compounded products
What is the importance of bioequivalence in drug approval?
when applying to produce a generic drug, bioequivalence (similar rate and absorption) must be proven
What are the two keys of bioequivalence?
-want a similar rate (Cmax) of absorption
-want a similar extent (area under curve) of absorption
