E1 L1: IV Bolus

Question 1

PK definition

Answer 1

The study of the process by which a drug is absorbed, distributed, metabolized, and excreted by the body (what the BODY does to the DRUG)

Question 2

ADME

Answer 2

Absorption (Small intestine)
Metabolism (Liver)
Distribution (Systemic circulation)
Excretion (Kidney, other tissues)

Question 3

Two major elimination pathways

Answer 3

Hepatic metabolism
Renal excretion

Question 4

PK goal

Answer 4

Optimal drug therapy - determination of optimal dosage regimen, e.g. how many mg and how many times a day

Question 5

• is our window to the body in pK

Answer 5

Blood

Question 6

IV bolus purpose

Answer 6

Rapid injection - ensures that the entire dose enters the systemic circulation Immediately

Question 7

One compartment model assumptions

Answer 7

Body acts like a single homogeneous compartment and drug rapidly distributes uniformly in it
The drug is in rapid equilibrium between the blood and the tissues
Changes in the plasma concentration of drug will result in proportional changes in tissue drug levels

Question 8

1 compartment model use

Answer 8

Blood compartment alone is sufficient to explain drug disposition

Question 9

Multi-compartment model

Answer 9

One (blood) compartment alone is not sufficient to explain drug disposition. More than one (ie. multi) compartments are needed

Question 10

First order elimination

Answer 10

Elimination rate is proportional to the concentration (or amount of drug)
Ex: time: 1, amount eliminated 10, amount remaining, 90
Time 2: amount eliminated - 9, Amount remaining - 81, etc.

Question 11

Elimination rate constant (Kel)

Answer 11

Kel is the proportionality constant relating the rate of elimination and the amount of drug in the body
A drug specific property
Has units of time-1, eg. min or h-1

Question 12

Volume of distribution (Vd)

Answer 12

Vd is the proportionality constant relating the amount of drug in the body and drug concentration in plasma
IMMEDIATELY after an IV bolus dose,
A drug specific property
Has units of volume (mL, L)

Question 13

Q: 100mg of drug X admin via IV bolus. What would be the typically expected drug conc. in the blood taken right after the IV dose?
(Body Weight: 60Kg)
Blood Volume (5L)
A. 100 mg/5L = 20mg/L
B. >20mg/L
C. <20 mg/L

Answer 13

C: <20mg/L
Most drugs exhibit tissue distribution, starting immediately after the IV dose

Question 14

Different drugs show different - After a given dose, thus a different VD

Answer 14

CP0

Question 15

Hydrophilic compounds

Answer 15

Do NOT cross lipid bilayers readily
Higher C0 given a dose

Question 16

Lipophilic compounds

Answer 16

Better tissue distribution
Lower C0 given a dose

Question 17

Vd is a measure of

Answer 17

Drug distribution in the body

Question 18

One compartment IV bolus model equation

Answer 18

CP = Cp0 -e^-kt

Question 19

The proportionality constant relating the rate of drug elimination and the plasma concentration

Answer 19

Clearance (CL)

Question 20

Kel Vs CL

Answer 20

Large Kel = Large Clearance
Both tell us about drug elimination

Question 21

Represents the fractional rate of loss of drug from the body

Answer 21

Kel

Question 22

Kel vs CL (in depth explain)

Answer 22

Kel - fractional rate of drug loss from the body
CL - Volume of drug-containing plasma from which drug is COMPLETELY cleared

Question 23

Can CL exceed cardiac output

Answer 23

No (because drugs reach the drug-eliminating organs via the blood pumped by heart)

Question 24

T/F: Kel has a limit it can exceed

Answer 24

False - it has no limit that it can exceed

Question 25

Linear kinetics

Answer 25

If we double the dose, then the plasma concentration will double at each time point (straight line)

Question 26

Non-linear kinetics properties

Answer 26

Dose-dependent pk
It occurs when one (or more) of ADME processes shows saturation

Question 27

Non-linear kinetics ex

Answer 27

Hepatic metabolism of a drug is saturated in typical dose range

Question 28

Non-linear kinetics pharmacokinetic parameters are…

Answer 28

Dose dependent (CL and VD)

Question 29

Linear Q:
For a drug that has linear kinetics, if we double the dose, then the plasma conc will double at each time point.
When the dose is higher, VD will
A. Increase
B. Not change
C. Decrease

Answer 29

B. Not change - LINEAR kinetics = Vd is independent of concentration

Question 30

Q. T/F: In linear kinetics, AUC is proportional to dose

Answer 30

True

Question 31

Q: Linear: As time passes after drug admin, Kel will
A. Increase
B. Not change
C. Stay the same

Answer 31

B. Not change - linear = independent

Question 32

Q. T/F - IV bolus: Kel from the data may be of a negative value

Answer 32

False - Kel cannot be negative

Question 33

Q. Linear IV bolus - Which of the following dose NOT increase proportionally with the dose
A. Drug concentration at time = 0
B. Drug concentration at time =4
C. AUC
D. Kel

Answer 33

C - AUC: measure of total exposure to drug over time