Pharmacokinetic Calculations

Question 1

What is the model used for the body during pharmacokinetic calculations?

Answer 1

• Assumes the body is a single vessel

Question 2

Describe what occurs in the one compartment model.

Answer 2

• Drug introduced rapidly at t=0
• Rapidly equilibrates through apparent Vd of body
• Drug eliminated by metabolism/excretion - drug concentration declines time dependently (decline usually exponential)

Question 3

What is Kel?

Answer 3

• Elimination rate constant
• Fraction of drug eliminated per unit time

Question 4

Describe first order kinetics.

Answer 4

• Rate of elimination directly proportional to drug concentration
• Half-life is constant

Question 5

Describe zero-order kinetics.

Answer 5

• Plasma drug concentration not directly proportional to rate of metabolism
• Rate of metabolism independent of drug concentration
• Rate of metabolism is constant
• Drugs can build up in body and cause toxic side effects
• EXAMPLES - alcohol and aspirin

Question 6

Describe C and C0.

Answer 6

• C - concentration of drug in plasma
• C0 - initial concentration of drug in plasma when t=0. [MAXIMUM DRUG] in plasma

Question 7

What is clearance?

Answer 7

• The volume of plasma from which a substance is completely removed per unit time
• Measured in litres per hour and ml per min
• Rate of drug elimination/plasma concentration

Question 8

What is volume of distribution?

Answer 8

• Apparent volume in which drug distributed to provide same concentration as it currently is in blood plasma
• Amount of drug in body/plasma concentration

Question 9

Define half-life.

Answer 9

• Time taken for amount of drug’s active substance in body to reduce by half

Question 10

What is Vd affected by?

Answer 10

• Drug permeability across tissue barriers
• Binding within compartments i.e plasma protein binding
• pH partition

Question 11

How can Vd be calculated?

Answer 11

• Dose/ concentration of drug in plasma
• FOR IV, equals dose/ C0 since in IV, C0 = drug concentration in plasma

Question 12

What is the formula for half-life?

Answer 12

0.693/Kel
- Or by direct measurement from semi-logarithmic plot of plasma concentration versus time

Question 13

What is the formula for clearance?

Answer 13

• Kel x Vd
• If Kel not known, rearrange equation for half life so: (0.693/half-life) x Vd

Question 14

What is the intention of multiple dosages/ dosages at different intervals?

Answer 14

• Provide relatively constant drug plasma concentration within limits of therapeutic efficacy and toxicity

Question 15

What is the ‘steady state’ of a drug?

Answer 15

• Point where amount of drug administered exactly replaces amount of drug excreted

Question 16

What is the formula for steady state concentration?

Answer 16

(BIOAVAILABILITY X DOSE) / DOSING INTERVAL X CLEARANCE

Question 17

Usually after how many half-lives is the steady state attained?

Answer 17

4 to 5

Question 18

Describe the relationship between having a short half life and time required to reach a steady state.

Answer 18

• Shorter half life, more rapidly steady state is reached
• Require intravenous infusions to maintain continued presence of drug

Question 19

Describe the relationship between having a long half life and time required to reach a steady state.

Answer 19

• If half life long compared with dosing interval, drug markedly accumulates
• Chronic dosing allows therapeutic range achieved at steady state

Question 20

When might a loading dose be administered and how can it be calculated?

Answer 20

• If therapeutic concentration needs to be achieved rapidly
• Vd x steady state plasma concentration