6. Pharmacokinetic modelling. Principles of pharmacotherapy

Question 1

Pharmacokinetics describes changes in…

Answer 1

Plasma drug conc. over time

Question 2

Pharmacokinetic models

Answer 2

Relatively simple mathematic schemes that represent complex physiological spaces or processes

• Amount of drug in tissues is generally related to plasma conc.

Question 3

Zero-order elimination

Answer 3

Occur when therapeutic doses of drug exceed the capacity of elimination mechanisms

• Plot concaves upwards
• Constant amount of drug will be eliminated per unit time

Question 4

First-order elimination

Answer 4

Occurs when elimination systems are not saturated by drug (most drugs)

• Linear function of plasma drug conc.
• Elimination of a constant fraction of drug per unit time

Question 5

One compartment open model

Answer 5

Body seen as one continuous fluid phase into which drug is administrated & diffuses

Open (continuous loss of drugs from compartment due to metabolism & excretion)

Question 6

Half-life

Answer 6

Time taken for plasma drug conc. to be reduced by 50%

• Only applies to drugs eliminated by first-order kinetics
• Log plasma drug conc. vs. time profile for drugs fitting in one compartment
• Related to:
  
  • Elimination rate constant (k)
  • Volume of distribution (VD)
  • Clearance (CL)
• Drug eliminated in time interval equal to 5 half lives

Question 7

Two compartment open model

Answer 7

How the body mostly behaves

1. Rapid change in plasma conc.
2. Linear ↓ in log drug conc.
3. Central compartment → equilibrium
4. Peripheral compartment → equilibrium
5. Distribution
6. Elimination

Question 8

Two compartment open model: Rapid change in plasma conc.

Answer 8

Distribution phase

• Time required for drug to reach equilibrium distribution between central & peripheral compartment

Question 9

Two compartment open model: Linear ↓ in log drug conc.

Answer 9

Observed if elimination phase is first order

Question 10

Two compartment open model: Central compartment → equilibrium

Answer 10

• Blood
• Intestinal fluid
• Highly perfused organs (heart, liver, lung, kidney)

Question 11

Two compartment open model: Peripheral compartment → equilibrium

Answer 11

Less perfused organs

• Skin
• Bone
• Fat

Question 12

Two-compartment open model: Distribution

Answer 12

Exponential

Question 13

Two compartment open model: Elimination

Answer 13

Linear

Question 14

Non-compartment PK analysis

Answer 14

Artificial mathematics has no direct relationship to physiological space

• Dependent on estimation of total drug exposure, most often estimated by area under the curve methods

Question 15

Give the principles of pharmacotherapy

Answer 15

• Repeat administration
• Steady state
• Loading dose
• Maintenance dose

Question 16

Repeat administration

Answer 16

If the drug eliminated by first-order kinetics is administered repeatedly, average plasma conc. of drug will ↑ until mean steady state is reached

Question 17

Time interval required to reach steady state =

Answer 17

5 half-lives

Question 18

Steady state

Answer 18

Average between high point after administration and low point just before next administration

• To maintain dose range, must be equal to elimination rate

Question 19

Loading dose

Answer 19

= desired drug_plasma x VD

• After loading dose we give maintenance dose → Steady state

Question 20

Maintenance dose

Answer 20

= desired drug_plasma x CL

• Dose required per unit time to maintain desired steady-state level in plasma