6 – Clinical Pharmacokinetics

Question 1

Clinical pharmacokinetics

Answer 1

• Mathematical description of the time course of disposition (MADE) of drugs in the body

Question 2

One compartment model

Answer 2

• Simplest model
• Assumes body acts as a HOMOGENOUS single compartment
• True for many drugs that distribute rapidly (ex. highly lipophilic)
• Kel: elimination constant (slope)

Question 3

Log Cp (blood plasma concentration) vs. time graph: one-compartment model

Answer 3

• Linear=straight line
• Slope=Kel

Question 4

7 half lives=

Answer 4

• 99% of drug eliminated

Question 5

Two compartment model

Answer 5

• Most drugs
• Central and peripheral compartment
• Beta: elimination rate constant (slope)

Question 6

Log Cp (blood plasma concentration) vs. time graph: two-compartment model

Answer 6

• Kink in the line
• A, D phase, then M, E phase
• *lag for the drug to diffuse into all the tissues

Question 7

Physiologically-based pharmacokinetic (PBPK) models

Answer 7

• Only done for drugs that have odd pharmokinetics
• Usually very dangerous drugs and toxins with a narrow therapeutic window
• Look at each organ system in isolation

Question 8

First-order kinetics

Answer 8

• Elimination is proportional to Cp (blood plasma concentration)
• Cp vs. time graph = nice down curve
• Drug can start with first-order at lower doses and then ‘switch’ to zero order kinetics at higher doses (SATURATION of biotransformation enzymes)

Question 9

Zero-order kinetics

Answer 9

• Elimination is INDEPENDENT of Cp
• CONSTANT elimination
• Dangerous=at higher doses, risk of toxicity is significant
• Cp vs. time graph = straight
• Ex. ethanol: why breathalyzer is constant/accurate test

Question 10

Steady state (repeated dosing)

Answer 10

• Attained after ~4 half-times
• Time to steady state is INDEPENDENT of dosage

Question 11

Steady state concentrations are proportional to

Answer 11

• Dose/dosage interval
• Oral bioavailability (F) / clearance

Question 12

Fluctuations in steady state graph

Answer 12

• Proportional to dosage interval/half-time
• Blunted by slow absorption

Question 13

Single oral dose: Cp vs time graph

Answer 13

• Goes up (A,D) and then down (M, E)

Question 14

Influence of dose interval on steady state

Answer 14

• Want to try and stay between:
  o minimum effective concentration
  o maximum safe concentration
• *want to have it larger than not

Question 15

What do most drugs follow for compartment model and order?

Answer 15

• Two compartment model
• First-order kinetics