Exam 1 Bioavailability and Clearance 3

Question 1

What is the equation for F if we assume 100% intestinal absorption?

Answer 1

F = Qh / (Gh+fu*CLint)

Question 2

What is F for both low Eh and high Eh drugs?

Answer 2

low Eh drug → F = 1

high Eh drug → F = Qh / fu*CLint

Question 3

What is the summary for low Eh drugs?

Answer 3

1. drugs are not subject to first pass effect
2. F is close to 1
3. F is not affected by any of the changes in CLint, fu, or Qh
4. CLh is affected by changes in fu and CLint

Question 4

What is the summary for high Eh drugs?

Answer 4

1. drugs are subject to significant first pass effect
2. F is small
3. F is affected by the changes in CLint, fu, or Qh
4. CLh is proportional to Qh

Question 5

Would the info from the previous slides hold true if intestinal absorption is poor (like 10%)?

Answer 5

no → F is bioavailability and we assume that 100% is absorbed in the intestine

Question 6

What is the cutoff for significant/insignificant change?

Answer 6

10%

Question 7

For a low Eh drug with an inducer, what changes are significant and insignificant?

Answer 7

significant → Eh, CLh

insignificant → F

Question 8

For a high Eh drug, what changes are significant and insignificant?

Answer 8

significant → F

insignificant → Eh, CLh

Question 9

What is the only limiting factor for hepatic metabolism with high Eh drugs?

Answer 9

supply

Question 10

What is the relationship between CL and AUC?

Answer 10

they move in opposite directions so if CL increases, then AUC decreases

Question 11

What is the same between low and high Eh drugs?

Answer 11

CL/F = fu*CLint

Question 12

What are the factors affecting AUCiv and AUCpo for low Eh drugs?

Answer 12

AUCiv → fu, CLint

AUCpo → fu, CLint

Question 13

What are the factors affecting AUCiv and AUCpo for high Eh drugs?

Answer 13

AUCiv → Qh

AUCpo → fu, CLint

Question 14

Which of Qh, fu, or CLint does cimetidine influence on labetalol and in what direction?

Answer 14

decreased CLint → labetalol is high Eh drug so CL = Qh and cimetidine is an inhibitor so it would decrease the CLint

Question 15

Why does AUCpo show significant changes upon cimetidine co-administration whereas AUCiv shows minimal change?

Answer 15

AUCpo is governed by CL/F whereas AUCiv is governed by CL and there is significant change in F if labetalol is combined with cimetidine

Question 16

Why does AUCpo show significant changes in cirrhosis patients whereas AUCiv shows a minimal change?

Answer 16

the decreased CLint has no effect on CL but decreases CL/F which is why AUCpo shows significant changes → AUCiv is governed by CL while AUCpo is governed by CL/F

Question 17

What directional changes in AUCiv and CL are expected with an enzyme inhibitor and a low Eh drug?

Answer 17

AUCiv increases and CL decreases

Question 18

What directional changes in AUCpo and F are expected with an enzyme inhibitor and a low Eh drug?

Answer 18

AUCpo increases and CL decreases but F would remain the same

Question 19

For a low Eh drug, what are the changes to CL, AUCiv, F, and AUCpo if CLint increases, fu increases, and Qh increases?

Answer 19

CLint increases → CL increases, AUCiv decreases, F no change, AUCpo decreases
fu increases → CL increases, AUCiv decreases, F no change, AUCpo decreases
Qh increases → no change for all 4

Question 20

For a high Eh drug, what are the effects on CL, AUCiv, F, and AUCpo if CLint increases, fu increases, and Qh increases?

Answer 20

CLint increases → CL no change, AUCiv no change, F decreases, AUCpo decreases
fu increases → CL no change, AUCiv no change, F decreases, AUCpo decreases
Qh increases → CL increases, AUCiv decreases, F increases, AUCpo no change

Question 21

Assuming 100% oral absorption, co-administration of an enzyme inducer with a low Eh drug (Drug X) would…

Answer 21

significantly increase CLh of Drug X

Question 22

Assuming 100% oral absorption, co-administration of an enzyme inducer with a high Eh drug (Drug Y) would…

Answer 22

significantly decrease F of Drug Y

Question 23

Can a drug be a low Eh drug, yet still 100% metabolized to be eliminated (fe=0 so no renal excretion of parent drug)?

Answer 23

yes

Question 24

After IV administration of drug X at 100 mg dose, you find 100% (100 mg) of drug X in the urine as metabolites. What is fe of drug X?

Answer 24

0 → fe is the fraction of drug in urine unchanged as the parent drug and it would be 0 if 100% of the drug are the metabolites