Basic Pharmacokinetics

Question 1

What are the X2 rate of reaction orders of drug kinetics?

Answer 1

Zero order kinetics

First order kinetics

Question 2

What is the principle of zero order drug kinetics?

What is the formula given for this?

Answer 2

The drug is eliminated at a constant rate irrespective of the concentration of the drug at that particular time and is only dependant on the elimination rate constant (K).

ΔA / Δt = -K

A = drug concentration
t= time

Question 3

What is the principle of first order drug kinetics?

What is the formula given for this?

Answer 3

The rate of elimination of the drug is dependant on the elimination rate constant AND the concentration of drug at that particular time.

ΔA / Δt = -KA

A = drug concentration
t= time

Question 4

What symbol denotes the elimination rate constant?

What type of measurement is it and what are it’s units?

Answer 4

K

It is a rate measurement with the units (min^1)

Question 5

What type of kinetics do most drugs follow?

Name a drug that is an exception?

Answer 5

Most follow first order kinetics

Alcohol and phenytoin (an anti-seizure medication) follow zero order

Question 6

What does the concentration-time graph look like for zero order vs first order kinetics?

Which axis is which?

Answer 6

Zero order = a straight line

First order = curve from top left to bottom right

Y-axis = drug concentration
X-axis = time

Question 7

What are the options for drug compartments and how many phases of decline do each type show?

Answer 7

X1 compartment = shows X1 phase of decline (monophasic or monoexponential)

X2 compartment = shows X2 phases of decline (biphasic)

Question 8

What is meant by the half life of a drug?

Answer 8

The time it takes for the plasma concentration of the drug to decrease by half.

Question 9

What formula tells you the concentration of a drug at a specific time?

Answer 9

A = A0 exp (-Kt)

A = concentration of drug (what you are trying to find)
A0 = initial concentration of drug at t=0
exp = exponent
K = elimination rate constant
t = time (current)

Question 10

What happens to the concentration-time curve for a first order kinetic drug if you plot the ln (natural log) of the concentration instead?

Answer 10

It becomes linear ( \ )

Question 11

What does the gradient of the ln(concentration)-time graph represent?

Answer 11

The elimination rate constant (K)

Question 12

What can the y-intercept of the ln(concentration)-time graph be used to calculate?

Answer 12

The concentration of drug at time zero.

CAREFUL! It will give you the ln[A] value; e^value will = [A]

Question 13

Which formula links the half like of a drug (t1/2) and the elimination rate constant (K)?

Answer 13

t1/2= 0.693 / K

NB: 0.693 = ln2

Question 14

What are the X4 letters of the X4 phases of pharmacokinetics and what do they stand for?

Answer 14

A = absolution
D = distribution
M = metabolism
E = excretion

Question 15

What is the absorption phase?

Answer 15

The process where the drug moves from the site of administration to the site of action.

Question 16

In the distribution phase, what does Vd stand for and what is it?

Answer 16

Vd = volume of distribution

This is the total amount of drug dosed / the plasma concentration of the drug at t=0

Question 17

How would you calculate the Vd?

Answer 17

Take a sample at t=0 to work out the concentration of drug in the plasma and then divide the drug doses by the sample concentration.

MAKE sure to check for units!

Question 18

What are the X2 phases of metabolism?

Answer 18

Phase 1 and phase 2!!!

Question 19

What process is phase 1 metabolism and what does it do?

Answer 19

Oxidation -adding an oxygen to make it more water soluble/easier to excrete

Question 20

What process is phase 2 metabolism?

Answer 20

Conjugation = binding a conjugate group to make it more water soluble/easier to excrete

Question 21

In the excretion phase, what does Cl stand for and what is its formulas?

Answer 21

Cl = clearance = volume of plasma cleared of the drug per unit time

Cl(total)= Cl(hepatic)+ Cl(renal) + Cl(metabolic)

OR

Cl(total)= K x Vd

Question 22

Is a drug considered ‘cleared’ as soon as it enters the metabolic phase as well as the excretion phase?

Answer 22

Yes

Question 23

What does Eh stand for in terms of hepatic clearance and how is it calculated?

Answer 23

Eh = extraction ratio

It is calculated by the concentration of drug going into the liver - the concentration of drug leaving. It is given as a number between 0-1.

Question 24

How do you calculate the Cl(hepatic)?

Is this process the same for Cl(renal) (kidneys)?

Answer 24

Cl = Q x Eh

Calculate the Eh (extraction ratio)

Work out blood flow for that organ (Q) (1.4L/min)

Multiply them.

The process is the same for the kidneys but Q (blood flow) = 1.1L/min

Question 25

What does F stand for and what does it mean?

Answer 25

F = bioavailability = fraction of unchanged drug which reaches the systemic circulation

Question 26

What is F for IV dosing?

Answer 26

F = 100%

Question 27

What formula for F (bioavailability) links it to the extraction ratio?

Answer 27

F = 1 - Eh

Question 28

What is an alternative formula for F?

Answer 28

F = AUC(oral) / AUC(IV)

AUC = area under curve

Question 29

Name the key equations for this topic.

Answer 29

T1/2 = 0.693 x K

Vd = A (dose of A given) / A0 (concentration of A at time = 0)

Cl(total) = K x Vd
Cl(total) = dose / AUC

F = 1 - Eh
F = AUC(oral) / AUC(IV)