Pharmacokinetics Malarkey

Question 1

How can the change in concentration of plasma drug concentration?

Answer 1

C(t2) = C(t1) x e-Kt

Question 2

What type of input is an IV bolus?

Answer 2

No input, K

• no absorption
• all enters body in one go

Question 3

What type of input is an IV infusion, patch or depot injection?

Answer 3

Zero order, K0

- released over a period of time

Question 4

What type of input is an oral, inhaled, transdermal, intramuscular or sub-cutaneous injection?

Answer 4

First order

• rate changes over time
• amount of drug decreases over time

Question 5

What pharmacokinetic factors change if the same drug is administered?

Answer 5

Absorption changes

• DME stays the same
• distribution
• metabolism
• excretion

Question 6

What is the concentration of the drug in the body proportional to?

Answer 6

Dose

• referenced to a particular time after dosing
• 5 mins
• 10 mins etc
• two distinct doses
• second twice as much as the first
• proportional increase in amount (concentration) of drug in the body at the corresponding time point

Question 7

What is the rate of elimination of drug from the body proportional to?

Answer 7

Concentration of drug in the body

Question 8

How can K be calculated from concentration of drug being removed from the body?

Answer 8

Ct = Dose/V x e-Kt

Question 9

What is elimination half life?

Answer 9

Pharmacokinetic parameter that is defined as the time it takes for the concentration of the drug in the plasma or the total amount in the body to be reduced by 50%

Question 10

What is half life an important factor in?

Answer 10

Rate of elimination
Duration of action
Interval between doses
Time for steady state
Time for complete elimination

Question 11

What is the equation to calculate K from half life?

Answer 11

K = ln2 / t1/2

Question 12

What is the equation to calculate Clearance or Volume of Distribution from K?

Answer 12

K = CL/V

Question 13

What parameter will inform Css average levels?

Answer 13

Clearance

Question 14

What parameter will inform how long it takes to achieve steady-state?

Answer 14

Half life

Question 15

How do enzymes and transporters display first order and zero order kinetics?

Answer 15

First order = as substrate concentration increases the rate of reaction increases
Zero order = as enzyme/transporter becomes saturated, there is not further increase in rate of reaction

Question 16

What is volume of distribution?

Answer 16

Pharmacokinetic parameter that may be defined as the “apparent” volume into which the drug distributes in the body once equilibrium has been achieved

Question 17

What is an apparent volume?

Answer 17

Even after drug equilibrium through the body, the drug concentrations are not homogenous in the body’s tissues
- drug concentrations in plasma will not be the same as concentration in brain, liver, muscle, fat etc

Question 18

How can volume of distribution be determined?

Answer 18

Plasma drug concentrations after intravenous drug administration

Question 19

Why can’t volume of distribution be determined after oral dosing or an intramuscular injection?

Answer 19

Don’t know how much actually gets into the blood

Question 20

Why are drug concentrations not homogenous through the body tissues?

Answer 20

Tissues vary in their characteristics and perfusion
- bone is different from fat
- blood flow per gram weight of tissue
A drug’s physiochemical properties will mean it can permeate to varying extents
- some tissues more
- some tissues less
Tissues possess different kinds of transporters through which drugs may gain access to intracellular sites which they would not other be able to do based on simple membrane diffusion
Plasma and tissue binding of drugs

Question 21

What is Fu?

Answer 21

Fraction unbound

- total mass of drug in plasma that is unbound

Question 22

How can Fu be calculated?

Answer 22

Fu = drug concentration in plasma (free) / drug concentration in plasma (total)

Question 23

How long does it take to achieve equilibrium in different tissues?

Answer 23

The time to achieve equilibrium is the same for each tissue

Question 24

What is equilbrium?

Answer 24

Point at which drug throughout all tissues behaves kinetically the same

Question 25

Why does digoxin display two compartment disposition?

Answer 25

Plasma - compartment 1
Myocardium - compartment 2

Equilibrium between compartment 1 and 2
Levels decline in compartment 1
- elimination

Question 26

What is the effect of increased volume of distribution?

Answer 26

First order elimination rate decreases
Elimination half life becomes longer
Increased residence of drug in the body
- stays in the body for longer

Question 27

Why does the dose of gentamicin need to be measured carefully?

Answer 27

Adjust in patients with extracellular fluid accumulation
- oedema
V = [0.25 L/kg x IBW] + [excess third-space fluid volume]
- each 1kg of weight gain due to fluid accumulation represents an additional 1 L of volume
V can also increase in patients in septic shock or experiencing malnutrition

Question 28

Why is the volume of distribution reduced in patients with renal disease or taking quinidine?

Answer 28

Digoxin binds very strongly to Na/KATPase in heart
Renal disease
- less moved back to plasma
- apparent V is reduced

Question 29

What should the loading dose of digoxin be?

Answer 29

Based on knowledge of target concentration and volume of distribution

Question 30

What is clearance of a drug?

Answer 30

Measure the efficiency of elimination for a particular drug

- apparent volume of plasma from which all the drug is irreversibly removed per unit time