Clinical Pharmacokinetics Flashcards
What is the basic hypothesis of clinical pharmacokinetics?
A relationship exists btwn pharmacological effect of a drug & the concentration of that drug in systemic circulation
What are 3 key concepts of clinical pharmacokinetics?
- bioavailability (F)
- volume of distribution (V”D”)
- CLEARANCE
what is clearance?
CL; overall efficiency of drug removal from body
- CL = 100 mL/min means 100 mL of blood is cleared of that drug every minute
What is a one compartment model?
the simplest model; it assumes that the body acts as a homogenous single compartment
Which drugs is the one compartment model true for?
Many drugs that distribute rapidly (are highly lipophilic)
What is C”p”?
plasma concentration
What is C”0” in a one compartment model?
plasma concentration at time 0
What is K”el” in a one compartment model?
the elimination rate constant. determined from slope of Log C”p” vs time graph
What is the eqn for drug half-life in a one compartment model? (T”1/2”)
0.693/K”el”
What is the eqn for clearance in a 1 compartment model? (CL)
V”D” x K”el”
When is 99% of a drug eliminated?
7 half lives
What model do most drugs follow?
two compartment model
What are the two compartments in a two compartment model?
central (1) - blood stream
peripheral (2) - fat, muscle, organ systems, nervous tissue
What are A & B in a two compartment model?
y intercepts
What is alpha (a) in a two compartment model?
slope of distribution phase
what is beta (B) in a two compartment model?
slope of elimination phase
- (B) is the ELIMINATION RATE CONSTANT, aka K”el” in a one compartment model
What is the eqn for drug half-life in a one compartment model? (T”1/2”)
0.693/(B)
What is the eqn for clearance in a 1 compartment model? (CL)
V”D” x (B)
What are physiologically-based pharmacokinetic (PBPK) models?
Much more realistic models that look at all compartments (each organ system) individually; often used for v dangerous drugs or toxicants that dont behave normally & have a narrow therapeutic window
How do first order and zero order pharmacokinetics differ?
- 1st order: elimination is PROPORTIONAL to C”p”
- 0 order: elimination is independent of C”p” (CONSTANT ELIMINATION)
How do you get a drug to reach steady state?
- repeated dosing; attained after approx 4 half-times (multiples of elimination)
- time to steady state is independent of dosage
What are steady state concentrations proportional to?
- proportional to dose/dosage interval
- proportional to F (oral bioavailability)/CL
Describe fluctuations related to steady state dosing?
- proportional to dosage interval/half-time
- blunted by slow absorption
How does dose interval influence steady state?
- too frequent dose administration can lead to build up of the drug above the maximum safe concentration
- not frequent enough dose administration can lead to the drug concentration dropping below the minimum effective concentration between doses
