PK II

Question 1

Clearance (CL) equation

Rate of elimination equation

(They are related)

Answer 1

CL = Rate of elim/Drug conc in measured fluid
CL = Drug out/Drug in

Rate of elimination = Q(C in - C out)

Question 2

Extraction ration (E)

Definition & equation

Answer 2

A measure of an organ’s efficiency in eliminating a drug form systemic circ over a single pass thru the organ

E = CL/Q
E organ = CL organ/Q organ

Q = blood flow

Question 3

Hepatic extraction of drug from circ equation

Hint: rate of elimination

Answer 3

Extraction of drug form circulation = rate of elimination in liver

= Q(C in - C out)

Question 4

Large extraction capacity (E > 0.7) - ___________limited

Small extraction capacity ( E < 0.3) - __________ limited

Answer 4

(E > 0.7) —> Low Q —> Blood flow-limited

(E < 0.3) —> Low CL —> Metabolism-limited

Question 5

Apparent Volume of distribution (Vd) equation

Answer 5

Vd = Dose/Cp

= Drug in body/Amount drug in circ

Question 6

If you have a High Vd, what does that mean?

Low Vd, what does that mean?

Answer 6

High Vd —> Drug is highly distributed throughout body

Low Vd —> Low distribution of drug through out body, high amount of drug in plasma circulation

Question 7

Drug A diffuses freely btw blood and peripheral tissues (Vd = 10). Drug B bind avidly to plasma proteins. How does this affect Drug B Vd compared to Drug A? Drug C bind avidly to molecules in peripheral tissues. How does this affect Drug C Vd compared to Drug A?

A. Vd of Drug B and C is higher than Vd of drug A
B. Drug B has a higher Vd than Drug A; Drug C has lower Vd than Drug A
C. Drug B has a lower Vd than Drug A; Drug C has higher Vd than Drug A
D. No change in Vd

Answer 7

C.

Drug B - more drug in plasma - Lower Vd
Drug C - more drug in peripheral tissue - Higher Vd

Question 8

Half-life (t1/2) equation & definition

Answer 8

T1/2 = 0.7 X Vd/CL

Time req to reduce amount of drug in body by 1/2 during elimination

Question 9

Half-life is an indicator of:

A. Time required to reach steady state
B. Time req for drug to be removed from body
C. Rate of elimination
D. Means to estimate dosing interval
E. A, B, and C
F. A, B, and D
G. All of the above

Answer 9

F.

A, B, and D

Question 10

Dosing rate equations (2)

Answer 10

DR = CL X Css

DR = (CL X Css)/F

  F = bioavailability

Question 11

How many half life’s are necessary for drug to reach steady state?

A. 1
B. 2
C. 3
D. 4

Answer 11

D. 4

Question 12

Bioavailability (F) definition & equation

Answer 12

The fraction of active drug that reaches systemic circulation

DR = (CL x Css)/F

F = (CL x Css)/DR

Question 13

An IV drug has a bioavailability of 100%. The same drug given orally has an F = 50%. How must the dose be adjusted to accommodate the differences in bioavailability between the two modes of administration?

A. Same dose
B. Triple dose
C. Reduce dose by half
D. Double dose

Answer 13

D. Double dose

DR = 100/F

DR(IV) = 100/100 = 1
DR(Oral) = 100/50 = 2

Question 14

AUC

What is it?
What does it reflect?

Answer 14

Area under the plasma-conc time curve

Reflects the total body exposure to a dose of drug

Question 15

Estimation of clearance based on AUC

Measure of bioavailability based of AUC

Answer 15

CL = dose/AUC

F = AUC x dose

Question 16

Absolute bioavailability equation

Compares what types of drugs

Answer 16

F = (AUC oral x Dose IV) / (AUV iv x Dose oral)

Compares bioavailability of drug by Non-IV (oral) route with bioavailability of drug by IV route

Question 17

Relative bioavailability equation

What does it compare?

Answer 17

F = (AUC a x Dose b) / (AUV b x Dose b)

Compares bioavailability of two oral formulations of same drug

Question 18

Loading dose equation

Maintenance dose equation

Answer 18

LD = (Vd x Css desired) / F
Or LD = Vd x Cp

MDR = (Css desired x CL) / F

 MDR = Rate of elim @ SS

Question 19

What equation is loading dose equation related to?

Answer 19

Vd = dose/Cp

Question 20

Maintence dose calculation for intermittent dosing rate

Answer 20

MD = (Dosing rate x dosing interval) / F