IV Bolus Review

Question 1

What is pharmacokinetics (PK)?

Answer 1

The study of the process by which a drug is absorbed, distributed, metabolized, and excreted by the body.
* aka what the body does to the drug

For this class, we are focused on small molecule drugs (MW <1000)

Question 2

What are the major drug elimination pathways?

Answer 2

1. Hepatic metabolism
2. Renal Excretion

Question 3

Where in the body does absorption typically occur?

Answer 3

The drug in formulation is absorbed in the small intestine

Question 4

Where in the body is the drug metabolized?

Answer 4

The drug is metabolized in the liver

Question 5

What proteins can drugs be bound to when in systemic circulation?

Answer 5

albumin

Question 6

In systemic circulation, what are the two states the drug can be in?

Answer 6

1. Drugs bound to proteins (albumin)
2. Free Drug

Question 7

What is distribution in ADME? Does the drug need to be free or bound?

Answer 7

In ADME, distribution refers to the process by which a drug is transported from the bloodstream to various tissues and organs of the body. Only the free (unbound) drug is pharmacologically active and can cross cell membranes to reach target tissues. Bound drug acts as a reservoir, prolonging the drug’s presence in the body but not directly contributing to its therapeutic effect until it dissociates from the protein.

Question 8

Where does drug excretion typically occur?

Answer 8

Kidney

Question 9

Where is the drug distributed to?

Answer 9

Other tissues

Question 10

What is the window to the body in PK?

Answer 10

Blood (plasma drug conc)

Question 11

What is the optimal drug therapy?

Answer 11

Determination of optimal dosage regimen
* aka how many mg and how many times a day

Question 12

Is an IV bolus input a slow or rapid injection?

Answer 12

Rapid

Question 13

For IV bolus, does the entire dose enter the systemic circulation immediately?

Answer 13

Yes; Drug concentration is highest at time 0 and decreases as time increases

Drug enters the bloodstream immediately

Question 14

What are the assumptions for a one compartment model IV bolus?

Answer 14

• The body acts like a single homogenous 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 15

Summarize the one compartment model for IV Bolus.

Answer 15

A one-compartment model assumes the body acts as a single, uniform compartment where drug concentration declines over time due to metabolism and excretion.

Question 16

Why might we need a multi-compartment model for an IV Bolus?

Answer 16

One compartment (ex. blood) is not sufficient to explain drug disposition. More than one compartments are needed.
* Ex. Blood<–>Tissue

Question 17

What order process is elimination? What does this mean for drug elimination?

Answer 17

• Elimination is a first order process
• The elimination rate is proportional to the concentration (or amount) of the drug

Zero Order= -10 each row
First Order= 10%

Question 18

What does the variable Ao stand for?

Answer 18

The drug amount at time=0, dose

Question 19

What does the variable t stand for?

Answer 19

time

Question 20

What does the variable kel stand for?

Answer 20

Elimination rate constant
* The proportionality constant relating the rate of elimation and the amount of drug in the body
* A drug-specific property
* Has units of time^-1, min^-1, or h^-1

Question 21

dA/dt

Answer 21

Elimination rate

Question 22

What does the variable A stand for?

Answer 22

Drug amount in the body

Question 23

dA/dt=?

Answer 23

-kel x (A)

Question 24

A=

Answer 24

Ao x e^((-kel)(t))

Question 25

In a one compartment model, is the drug concentration in the compartment the same as the plasma drug concentration (blood)?

Answer 25

Yes!

Question 26

What is Vd?

Answer 26

The proportionality constant relating the amount of drug in the body and the drug concentration in the plasma. * A=Vd x Cp * In a one compartment model, the size of the compartment is Vd. * Immediately after an IV bolus dose, Dose= Vd x Cpo * a drug-specific property * Has units of volume (mL or L) | The measure of drug distibution in the body.

Question 27

100 mg of Drug X administered via IV bolus. What would be the typically expected drug X concentration in the blood be taken right after the IV dose (i.e., Cp0)? | Body Weight= 60 kg Blood Volume= 5 L

Answer 27

Dose = Vd x Cpo Dose/Vd= Cpo 100 mg/5L= 20 mg/L HW, the concentration for most drugs is much less, so the final answer is <20 mg/L ## Footnote Most (small molecule) drugs exhibit modest to significant tissue distribution, starting immediately after the IV dose.

Question 28

How do we determine which drug has better tissue distribution?

Answer 28

Whichever one has a LARGER Vd.

Question 29

What does Vd depend on?

Answer 29

The physicochemical properties of the drug. * Hydrophilic compinds do not cross lipid bilayers readily. Higher Co given a dose. * Lipophilic compounds have better tissue distribution. Lower Co given the same dose.

Question 30

How does Vd relate to the physiologic volume?

Answer 30

* In most cases, Vd dose not correspond to a physiologic volume * With extensive tissue distribution, Vd > 100 L is common and Vd > 10,000 L is possible. Special Circumstance: * If the drug is confined to the bloodstream (volume ~5 L) or total body water (volume ~42 L), then the PK parameter Vd may reflect the physiologic volume.

Question 31

Cp=

Answer 31

Cpo x e^((-kel)(t))

Question 32

What is a half-life?

Answer 32

The time it takes for half of the drug in the body to be eliminated or the time it takes for the plasma concentration to decrease by a half * Units are time (s, h, min)

Question 33

t1/2=

Answer 33

0.693/kel

Question 34

How do we calculate the fraction of the dose remaining in the body?

Answer 34

Two ways: * e^(-kel)(t) * (1/2)^n; n= # of half lives

Question 35

Fraction of dose eliminated from the body=

Answer 35

Two ways: * 1-e^(-kel)(t) *1-(1/2)^n

Question 36

What is clearance (CL)?

Answer 36

The proportionality constant relating the rate of drug elimination and the plasma concentration. * Units of volume per unit of time (ml/min, L/h)

Question 37

dA/dt=

Answer 37

-Cl x Cp

Question 38

CL=

Answer 38

Kel(Vd) or Dose/AUC

Question 39

What is Kel in words related to elimination?

Answer 39

Fractional rate of drug loss from the body

Question 40

What is CL in words related to elimination?

Answer 40

Volume of drug-containing plasma from which drug is completely cleared.

Question 41

T or F: Theoretically, CL cannot exceed cardiac output (because drugs reach the drug-eliminating organs via the blood pumped by heart)

Answer 41

True

Question 42

What characterizes linear kinetics?

Answer 42

* For a drug that has linear kinetics, if we double the dose then the plasma concentration will double at each time point. * Pharmacokinetic parameters (k, CL, or Vd) are constant, that is, they are independent of dose

Question 42

What characterizes non-linear kinetics?

Answer 42

* Dose-dependent PK * It occurs when one (or more) of ADME processes shows saturation * Ex. hepatic metabolism of a drug is saturated in typical dose range. * Pharmacokinetic parameters (clearance and volume of distribution) are dependent of dose * For example, half life at an earlier time point is longer than the half life at a later time point.

Question 43

Does the rate constant Kel change when dose changes?

Answer 43

NO