PK Principles

Question 1

What is pharmacokinetics and pharmacodynamics

Answer 1

Pharmacokinetics: Time course of drugs in the body

Pharmacodynamics: Temporal relationship between drug concentration (at site of action) and pharmacological effect

Question 2

Show the plasma concentration-time profile of a Oral Drug

Answer 2

Question 3

Show the plasma concentration(log)-time profile of a Oral Drug

Answer 3

Question 4

Show the plasma concentration-time profile of a IV bolus injection

What does initial concentration (C_{0<strong>​</strong>}) depend on

Answer 4

Initial concentration (C₀) depends on Dose (D) and Volume (V) of reservoir

C₀= D/V

Question 5

For Volume of distribution

A) What are its volumes

B) What is the physiological volumes?

C) What is the pharmacokinetic volumes?

Answer 5

A)

• Considered to be a “dilution volume”
• Units – ‘volume’ (Litres)
• Normalised – L/kg

B)

• Plasma ~ 3L
• Extracellular fluid ~ 16L
• Total body water ~ 42L

C)

• Gentamicin = 0.26 L/kg (17L)
• Mefloquine = 20 L/kg (1,400L)

Question 6

For Clearance (CL)

A) What does it depend on?

B) What is the equation

C) How to define it

D) What are some physiological values

Answer 6

A)

Clearance (CL) of drug depends on rate of blood flow (Q) through organ and extraction efficiency (E) of organ

B)

CL = Q x E

• Q = blood flow
• E = extraction ratio
• Units are volume per time (L/hr)
• Normalised – L/hr/kg or mL/min/kg

C)

Volume of blood or plasma that is cleared of drug in a given unit of time

D)

• Kidneys ~ 1.1 L/min (0.9 L/kg/hr)
• Liver ~ 1.35 L/min (1.1 L/kg/hr)

Question 7

What is elimination rate constant (k)? (Pharmacokinetic paramteters) Provide the formula

Answer 7

• ‘fractional rate of elimination
• units are ‘reciprocal time’, e.g. hr^-1
• consider: k = 0.1 hr^-1​

> 10% of drug in the body is eliminated per hour (not plasma concentration)

start with 100 mg → 90 mg (1 hr) → 81 mg (2 hr) → 73 mg (3 hr) → 66 mg (4 hr) etc

• consider: k = 0.2 hr^-1

> start: 100 mg → 80 mg (1 hr) → 64 mg (2 hr) → 51 mg (3 hr) → 41 mg (4 hr) etc.

CL = k ×V –> k = CL/V

Question 8

What is the formula for the elimination rate constant for a normal plasma concentration time profile of a normal drug

Answer 8

C = C₀ x e^-kt

drug elimination is usually exponential, or “first order”

Question 9

What is the formula for the elimination rate constant for a logarithmic plasma concentration time profile of a normal drug

Answer 9

Question 10

How to calculate half-life for the elimination rate constant for a plasma concentration time profile of a normal drug

Answer 10

Time for plasma concentration to fall by one half

Question 11

How to calculate one compartment models?

Answer 11

Question 12

How to calculate two compartment models

Answer 12

Question 13

Calculation of PK parameters is ‘model independent’ or ‘non-compartmental’

What does this mean

Answer 13

Based on Dose and AUC (area under the plasma concentration-time curve)

• Commence with ‘Area under the plasma concentration-time curve’ or AUC, and the elimination half-life (t^½) or k
• Using Dose, AUC and k, other parameters including CL & V can be determined and used to calculate doses for patients
• AUC is calculated from the actual plasma concentration-time data
• k and t½ also determined from the data

Question 14

For plasma concentration-time data: discuss AUC

Answer 14

Question 15

What is the Trepzoidal method? What are some equations associated with it?

Answer 15

Question 16

Discuss plasma concentration-time data

Answer 16

Question 17

Trapezoidal method —> intravenous data? Provide the graph and formula

Answer 17

Question 18

Give a summary of the calculation of PK parameters

Answer 18

Question 19

Provide a summary of the linear trapezoidal method

Answer 19