EXAM 1- Dr. K

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List some examples of Extravascular routes of administration:

• examples: oral, SQ, IM, and transdermal, rectal, vaginal

• ANYTHING NOT IV!!!!!!!!!!!!

How is EV administration different from IV administration in terms of where the drug enters and bioavailability?

IV admin: drug ENTERS systemic circulation, 100% bioavailable.

EV admin: drug DOES NOT ENTER systemic circulation DIRECTLY, <100% bioavailable

When drugs are taken orally, the drug molecules absorbed from the GI tract are susceptible to _____________________ generally lowering bioavailability.

first pass metabolism

Does this PK graph represent an IV or EV administration?

IV

Does this PK graph represent an IV or EV administration?

EV

What’s the difference between C_pmax and T_max for EV and IV administration?

EV admin: Cpmax will be lower than IV, and Tmax will NOT occur at t=0

IV admin: Cpmax is higher, Tmax is at t=0

Why is the Cpmax and Tmax different in IV and EV administration?

It is different due to the EV administration having an ABSORPTION phase

What factors can affect the absorption phase of EV administration?

• physiochemical properties of the drug molecule

• nature of the membrane

• physiological factors

Which of the following is in the correct order by which they occur:

a. disintegration, diffusion, dissolution

b. dissolution, disintegration, diffusion

c. disintegration, dissolution, diffusion

d. diffusion, dissolution, disintegration

c

We assume that oral administered drugs follow what type of model?

a. one compartment

b. two compartment

a

We assume that oral administered drugs follow what type of process?

a. zero order process

b. first order process

c. second order process

b

Ka represents the ______________ constant.

absorption rate

Ke represents the ____________________ constant.

elimination rate

True or false: As the amount of drug remaining to be absorbed decreases with time, so does the rate of absorption.

true (1st order kinetics)

For an oral dosage form, which of the following is true during the absorption phase? (before the peak)

a. Ka > Ke

b. Ka= Ke

c. Ka < Ke

d. Ke > Ka

(disclaimer: should be the RATES not the rate constants, but I’m too lazy to change it)

a (MORE DRUG IS BEING ABSORBED THAN ELIMINATED)

For an oral dosage form, which of the following is true during the elimination phase? (after the peak)

a. Ka > Ke

b. Ka= Ke

c. Ka < Ke

d. Ke < Ka

(disclaimer: should be the RATES not the rate constants, but I’m too lazy to change it)

c (MORE DRUG IS ELIMINATED THAN IS ABSORBED)

What does the peak of the PK curve of an oral DF represent?

a. Cmax

b. Tmax

c. both a and b

c

What happens at the peak or Tmax on a PK curve of an oral dosage form?

a. Ka > Ke

b. Ka= Ke

c. Ka < Ke

d. Ke < Ka

(disclaimer: should be the RATES not the rate constants, but I’m too lazy to change it)

b

True or False: Elimination begins as soon as a drug reaches circulation.

true

Using the attached equation solve the following problem:

Drug Y (150 mg) is given as an oral solution and has the following pk parameters:

• t1/2= 8hr

• Ka= 0.25h

• Vd= 10L

• F=1

What will be the plasma concentration at 12 hours after the dose is administered?

What does lag time (t₀) indicate?

that absorption has not started immediately following the administration of a drug by oral or other EV routes of administration

What factors might delay absorption and cause lag time?

• disintegration

• dissolution from DF

• incomplete wetting

• slow dispersion

• poor formulation

Unless the body produces the drug, ____________ is not possible.

negative lag time (-t₀)

If neg lag time is calculated it may be due to…

• lack of data

• Ka is not much larger than Ke

• error

(basically: think that negative lag time would mean that the body absorbed the drug before it was even administered… DOESN’T MAKE SENSE RIGHT??? so it’s probably due to error!!!!)

Does absorption rate constant change due to route of administration? Does elimination rate constant change due to route of administration?

• absorption rate CHANGES due to route of administration

• elimination rate DOES NOT CHANGE or is INDEPENDENT of route of administration

List things that might change absorption rate:

• route of administration

• formulation

• dosage form

How is elimination half-life, elimination rate constant, apparent volume of distribution and clearance effect by route of administration?

ALL OF THESE ARE INDEPENDENT OF ROUTE OF ADMINISTRATION

(think about it like this: if i switch from oral to topical, why would the volume of distribution which is a set amount in our body change?)

The onset of action, duration of action, and termination action are influenced by…

• formulation

• dosage form

• route of administration

PRACTICE:

Which of the following would not be influenced if I changed the route of administration?

a. absorption rate

b. elimination half life

c. onset of action

d. duration of action

b

___________ is the time which the body displays maximum plasma concentration (Cpmax).

Tmax

Is Tmax independent or dependent of dose administered?

INDEPENDENT

Is Cpmax independent or dependent of dose administered?

DEPENDENT

Is Cpmax directly or indirectly proportional to the amount of drug reaching circulation and administered dose? If I increased the dose, what would happen to Cpmax?

directly proportional; if I increased the dose, I would increase Cpmax

If I administered the same dose in a patient that is healthy versus renally impaired, where would you expect to see the biggest change?

a. Ka

b. Ke

c. Cpmax

d. Tmax

b. Ke

True or False: the fraction absorbed (F) is constant for given formulation, dosage form, and route of administration and will still remain constant if any of those factors are changed.

false—> fraction absorbed (F) WILL CHANGE (not remain constant) if formulation, dosage form, or ROA is changed