Clinical Pharmacokinetics

Question 1

What is the basic hypothesis of clinical pharmacokinetics?

Answer 1

A relationship exists btwn pharmacological effect of a drug & the concentration of that drug in systemic circulation

Question 2

What are 3 key concepts of clinical pharmacokinetics?

Answer 2

1. bioavailability (F)
2. volume of distribution (V”D”)
3. CLEARANCE

Question 3

what is clearance?

Answer 3

CL; overall efficiency of drug removal from body
- CL = 100 mL/min means 100 mL of blood is cleared of that drug every minute

Question 4

What is a one compartment model?

Answer 4

the simplest model; it assumes that the body acts as a homogenous single compartment

Question 5

Which drugs is the one compartment model true for?

Answer 5

Many drugs that distribute rapidly (are highly lipophilic)

Question 6

What is C”p”?

Answer 6

plasma concentration

Question 7

What is C”0” in a one compartment model?

Answer 7

plasma concentration at time 0

Question 8

What is K”el” in a one compartment model?

Answer 8

the elimination rate constant. determined from slope of Log C”p” vs time graph

Question 9

What is the eqn for drug half-life in a one compartment model? (T”1/2”)

Answer 9

0.693/K”el”

Question 10

What is the eqn for clearance in a 1 compartment model? (CL)

Answer 10

V”D” x K”el”

Question 11

When is 99% of a drug eliminated?

Answer 11

7 half lives

Question 12

What model do most drugs follow?

Answer 12

two compartment model

Question 13

What are the two compartments in a two compartment model?

Answer 13

central (1) - blood stream
peripheral (2) - fat, muscle, organ systems, nervous tissue

Question 14

What are A & B in a two compartment model?

Answer 14

y intercepts

Question 15

What is alpha (a) in a two compartment model?

Answer 15

slope of distribution phase

Question 16

what is beta (B) in a two compartment model?

Answer 16

slope of elimination phase
- (B) is the ELIMINATION RATE CONSTANT, aka K”el” in a one compartment model

Question 17

What is the eqn for drug half-life in a one compartment model? (T”1/2”)

Answer 17

0.693/(B)

Question 18

What is the eqn for clearance in a 1 compartment model? (CL)

Answer 18

V”D” x (B)

Question 19

What are physiologically-based pharmacokinetic (PBPK) models?

Answer 19

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

Question 20

How do first order and zero order pharmacokinetics differ?

Answer 20

• 1st order: elimination is PROPORTIONAL to C”p”
• 0 order: elimination is independent of C”p” (CONSTANT ELIMINATION)

Question 21

How do you get a drug to reach steady state?

Answer 21

• repeated dosing; attained after approx 4 half-times (multiples of elimination)
• time to steady state is independent of dosage

Question 22

What are steady state concentrations proportional to?

Answer 22

• proportional to dose/dosage interval
• proportional to F (oral bioavailability)/CL

Question 23

Describe fluctuations related to steady state dosing?

Answer 23

• proportional to dosage interval/half-time
• blunted by slow absorption

Question 24

How does dose interval influence steady state?

Answer 24

• 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

Question 25

What is a good examples of steady state dosage?

Answer 25

Antibiotics

Question 26

Why are drugs exhibiting zero order pharmacokinetics dangerous?

Answer 26

because elimination is constant, thus at higher doses the risk of toxicity can be significant

Question 27

How can a drug exhibit first order kinetics @ lower doses and then “switch” to zero order kinetics at higher doses?

Answer 27

this is due mainly to saturation of the biotransformation enzyme