pharmacokinetics Flashcards
4 Principles of Pharmacokinetics
Absorption
Distribution
Metabolism
Elimination
Variable affecting absorption
bioavailability
variable affecting distribution
volume of distribution
variable affecting metabolism
half-life
variable affecting elimination
clearance
Bioavailability (F) Definition
the fraction of unchanged (still active) drug that reaches the systemic circulation
F = 100% when:
the drug is administered directly into a patient’s blood vessels
- IV, IA, PICC
F < 100% when:
some of the drug is lost before reaching the heart
How can F < 100%?
a. some of the drug is lost before instestinal absorption
b. lost by modification of the drug by intestinal/ hepatic metabolism (enzymes)
c. lost because transporters return the drug to the gastrointestinal tract (into bile, SI)
How is bioavailability calculated?
by comparing the amount of drug absorbed over time from the route of administration of interest to the amount of drug absorbed over time when the same dose is giver by the IV route
the Area Under the Curve (AUC) is directly proportional to:
the dose administered and the bioavailability of the drug
A large curve (AUC) =
a large dose
slow clearance
a large dose =
a large area under the curve (AUC)
a small area under the curve (AUC) =
a small dose
fast clearance
a small dose =
a small area under the curve (AUC)
AUC is inversely proportional to:
the clearance of the drug
fast clearance of the drug =
small area under the curve (AUC)
slow clearance of the drug =
large area under the curve (AUC)
Factors affecting bioavailability: (5)
- Gastrointestinal System Motility
- Gastrointestinal Surface Area
- Hepatic Metabolism
- pH of liquid surrounding the drug
- Drug Interactions
Factors affecting bioavailability: Gastrointestinal System Motility
a. rate of gastric (stomach) emptying
b. rate of intestinal emptying (intestinal motility)
Slow gastric emptying =
reduced bioavailability of the drug
- reduced SA in stomach for
absorption
- destruction by low pH in
stomach + gastric enzymes
Fast gastric emptying
increased bioavailability of the drug
- less time in stomach
subjected to low pH + gastric
enzymes
- moves to an area with
increased SA for absorption
Low intestinal motility (stasis) =
increased bioavailability
- more time to interact with SA
and be absorbed
- low pH, not destroyed
Fast intestinal motility (diarrhea) =
reduced bioavailability
- less time to interact with SA
and be absorbed
- often discarded in full, no time
to reach therapeutic
minimum