Introduction into Pharmacokinetics Flashcards
What is pharmacokinetics?
the process by which a drug is absorbed, distributed, metabolized, and excreted
Typically, what are drug concentrations measured in?
plasma
What is oral availability (F)?
the fraction of the drug that reaches the systemic circulation after oral ingestion
What is oral availability determined by?
absorption and first pass metabolism
What does absorption refer to?
the ability of a drug to cross the gut wall into the portal vein
What is first-pass metabolism?
the presystemic drug elimination
Where can first-pass metabolism occur?
in the gut wall, portal vein, or the liver
High rates of metabolism in the gut wall, portal vein, or liver result in what?
low oral availability
What is the total amount of the drug in the systemic circulation defined by?
the area under the concentration time curve (AUC)
What is bioavailability?
the fraction of a drug that is absorbed and available to produce its systemic effect
What does it mean if bioavailability is low?
it means that few drug molecules go to the plasma, meaning low drug effect
What leads to low drug availability?
high metabolism or low absorption
What percent bioavailability do you want to make sure you get an effect and that it is safe?
60-70%
What is plasma concentration (Cp) directly proportional to? inversely proportional?
dose rate, clearance
What is the steady state concentration (Cpss) determined by?
the maintenance dose rate and the clearance
For drugs with a high fu (unbound fraction) will renal impairment or liver impairment decrease the clearance?
renal impairment
For lipophilic drugs with low fu, will renal impairment or liver impairment decrease the clearance?
liver impairment
What must be adjusted to allow for impaired drug clearance?
dosage
How are drugs eliminated?
by excretion unchanged through the kidneys, or by metabolism to an inactive product usually in the liver
What does fraction excreted unchanged (fu) define?
renal elimination
What does (1-fu) describe?
metabolic elimination
What are the different types of clearances?
whole body (blood, plasma), organ clearance, and in vitro clearance
What is the objective of the interspecies dose extrapolation?
to ensure similar exposure (AUC) between species
What is the assumption with the interspecies dose extrapolation?
that the axposure response relationship is not species specific
Drug exposure is on the ______ _____.
causal chain
Since little can be modified on the interactionof exposure and response (what happens inside the body), what can you do to optomize exposure?
change the amount of input of the drug
