Exam 1 Bioavailability and Clearance 3 Flashcards
What is the equation for F if we assume 100% intestinal absorption?
F = Qh / (Gh+fu*CLint)
What is F for both low Eh and high Eh drugs?
low Eh drug → F = 1
high Eh drug → F = Qh / fu*CLint
What is the summary for low Eh drugs?
- drugs are not subject to first pass effect
- F is close to 1
- F is not affected by any of the changes in CLint, fu, or Qh
- CLh is affected by changes in fu and CLint
What is the summary for high Eh drugs?
- drugs are subject to significant first pass effect
- F is small
- F is affected by the changes in CLint, fu, or Qh
- CLh is proportional to Qh
Would the info from the previous slides hold true if intestinal absorption is poor (like 10%)?
no → F is bioavailability and we assume that 100% is absorbed in the intestine
What is the cutoff for significant/insignificant change?
10%
For a low Eh drug with an inducer, what changes are significant and insignificant?
significant → Eh, CLh
insignificant → F
For a high Eh drug, what changes are significant and insignificant?
significant → F
insignificant → Eh, CLh
What is the only limiting factor for hepatic metabolism with high Eh drugs?
supply
What is the relationship between CL and AUC?
they move in opposite directions so if CL increases, then AUC decreases
What is the same between low and high Eh drugs?
CL/F = fu*CLint
What are the factors affecting AUCiv and AUCpo for low Eh drugs?
AUCiv → fu, CLint
AUCpo → fu, CLint
What are the factors affecting AUCiv and AUCpo for high Eh drugs?
AUCiv → Qh
AUCpo → fu, CLint
Which of Qh, fu, or CLint does cimetidine influence on labetalol and in what direction?
decreased CLint → labetalol is high Eh drug so CL = Qh and cimetidine is an inhibitor so it would decrease the CLint
Why does AUCpo show significant changes upon cimetidine co-administration whereas AUCiv shows minimal change?
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
Why does AUCpo show significant changes in cirrhosis patients whereas AUCiv shows a minimal change?
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
What directional changes in AUCiv and CL are expected with an enzyme inhibitor and a low Eh drug?
AUCiv increases and CL decreases
What directional changes in AUCpo and F are expected with an enzyme inhibitor and a low Eh drug?
AUCpo increases and CL decreases but F would remain the same
For a low Eh drug, what are the changes to CL, AUCiv, F, and AUCpo if CLint increases, fu increases, and Qh increases?
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
For a high Eh drug, what are the effects on CL, AUCiv, F, and AUCpo if CLint increases, fu increases, and Qh increases?
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
Assuming 100% oral absorption, co-administration of an enzyme inducer with a low Eh drug (Drug X) would…
significantly increase CLh of Drug X
Assuming 100% oral absorption, co-administration of an enzyme inducer with a high Eh drug (Drug Y) would…
significantly decrease F of Drug Y
Can a drug be a low Eh drug, yet still 100% metabolized to be eliminated (fe=0 so no renal excretion of parent drug)?
yes
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?
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
