Pharmacokinetics

Question 1

Why is PK important?

Answer 1

ADME (absorption, distribution, metabolism, excretion)
Determines species specific drug behavior, arrives safe and effective doses, optimization of therapeutic concentration

Question 2

Area under curve (AUC)

Answer 2

Expresses the total amount of drug that comes into the systemic circulation after administration

Question 3

Why is AUC important?

Answer 3

Evaluates bioavailibility of a drug from its dosage form
Represent the extent of absorption

Question 4

Bioequivalence

Answer 4

Comparing the generic version of a drug to a new one
C max and T max should be relatively equal

Question 5

Volume of distribution

Answer 5

Vd= Dose (amount given) / Plasma concentration

Question 6

When is there high Vd?

Answer 6

High tissue distribution
Low plasma tissue binding
More lipid soluble
Mainly in tissues

Question 7

When is there low Vd?

Answer 7

Low tissue distribution
More water soluble
Mainly stays in plasma
High plasma concentration
High protein binding drugs

Question 8

How do you determine dose?

Answer 8

Dose= Vd x target concentration

Question 9

Vd of protein bound drugs

Answer 9

Limited to plasma
5% of body weight= 0.05 L/ kg

Question 10

Vd of water soluble drugs

Answer 10

In extracellular fluid
20-30% of body weight=0.2-0.3 L/kg

Question 11

Vd of lipid soluble drugs

Answer 11

Distributed in plasma
ECF and intracellular fluid (ICF) or total body water (TBW)
60-70% of body weight= 0.6-0.7 L/kg

Question 12

Example for finding dose

Answer 12

Pentobarbital= highly LIPID SOLUBLE anesthetic agent
Vd= 0.6 L/ kg , target conc = 20 mg/L (given with drug)
Dose= 0.6 L/kg x 20 mg/L = 12 mg/kg

Question 13

Elimination rate constant (k)

Answer 13

Fraction of the drug in the body removed per unit time
OR
Rate where plasma concentration declines during elimination phase

Question 14

Zero order (drug elimination)

Answer 14

A fixed amount/ quality of drug processed per unit time
Ex: alcohol, phenytoin and salicylates

Question 15

What does half-life of zero-order kinetics depend on?

Answer 15

On the dose administration (higher dose, higher half-life)

Question 16

Examples of drugs in zero order

Answer 16

Salicylates in cats
Phenylbutazone in dogs and horses
half-life dose dependent

Question 17

First order (drug elimination)

Answer 17

A fixed fraction or % of drug processed per unit time
Half life constant even with increased dose
Most drugs

Question 18

For first order, when does complete elimination occur?

Answer 18

5 half-lives

Question 19

Half-life

Answer 19

Time taken for the drug concentration to fall to half it’s original value
t1/2= 0.693 x Vd/CL

Question 20

Short half-life

Answer 20

Indicates short duration (rapid elimination) and low concentration at the site of action

Question 21

Why is half-life useful?

Answer 21

For determining an appropriate dosing interval
Determines time taken to achieve a steady state or equilibrium constant with any constant dose rate

Question 22

Which drugs will have a long half-life?

Answer 22

Drugs widely distributed and sequestered in tissues

Question 23

Which will increase half-life?

Answer 23

Enter-hepatic circulation and plasma protein binding
Renal and hepatic dysfunctions depending on route of elimination

Question 24

Dosing interval

Answer 24

Time interval between doses that keeps plasma concentration of a drug within therapeutic range

Question 25

How is dosing interval determined?

Answer 25

Max plasma concentration(Cmax) to drop below where desired response no longer occurs (MEC,Cmin)

Question 26

What is recommended for therapeutic pruposes?

Answer 26

A dosing interval equal to or less than the elimination half-life

Question 27

Steady state concentration

Answer 27

Time where concentration remains stable OR consistent when drug is given repeatedly or continuously.
Ex: IV infusion

Question 28

When do you reach steady state?

Answer 28

When the rate of drug entering systemic circulation equals the rate of elimination
Approximately in 3-5 half-lives

Question 29

One compartment

Answer 29

Whole body a single homogenous unit
Rapidly distributed drugs

Question 30

Two compartments

Answer 30

Central comp- highly perfused organs
Peripheral comp- less perfused organs

Question 31

Non-compartments

Answer 31

No assumption of any compartment
Derives pharmacokinetic parameters by simple algebraic equations