L37 - Drug Elimination - Metabolism 2 Flashcards
What is hepatic extraction ratio defined as?
- fraction of drug passing by liver which is eliminated
- ratio between rate of hepatic elimination and rate of presentation of drug to the liver
What is the eqn for hepatic extraction rate?
Eh = rate of elimination / rate of presentation
= Centering - Cleaving)/Centering
What is the eqn for rate of drug presentation?
Qh x Centering
What is the eqn for drug elimination?
Qh x (Centering - Cleaving)
What and when does the extraction ratio range?
- 0, drug not eliminated / Centering = Cleaving
- 1 all drug eliminated / Cleaving = 0
What is the hepatic extraction ratio a measure of?
The liver efficiency in eliminating the drug from the systemic circulation over a single pass through the organ
What does hepatic clearance (CIh) measure?
The loss of drug across the liver
What can CIh be defined as?
- volume of blood entering the liver from which all the drug is removed per unit time
- ratio between hepatic elim rate and incoming conc
What does some drugs the time required for…?
- leaving blood cells
- dissocating from plasma proteins
- diffusing hepatic membranes
- being metabolised
- being transported to bile
What is hugh extraction rate?
Extraction ratio between 0.7-1
What is high extraction rate like?
- partition out from blood cells, dissociation from plasma proteins, passage through membranes to bile very fast
- elimation process dependent on blood bringing more drug (clearance is perfusion rate limited)
What is hepatic clearance like in high extraction rate?
- hepatic clearance approaches blood flow
- very sensitive to changes in blood flow
- insensitive to changes in plasma binding, enzymatic interactions
What do drugs with high hepatic extraction ratio usually have?
Low systemic absorption, bc metabolsied extensively by first pass effect
Why can some drugs have low extraction rate?
- slow dissociation from RBC
- slow dissociation from plasma protein
- slow diffusion from plasma proteins
- slow diffusion into hepatocytes
- most frequent - slow enzymatic reaction
- slow transport into bile
What is low extraction ratio?
Exctraction ratio <= 0.3
What is low extraction rate like?
- parition out from blood cells, or dissociation from plasma proteins or passage through membranes into bile is slow
- poor efficiency of the liver eliminating the drug
What is hepatic clearance like in low extraction rate?
- sensitive to changes plasma binding, enzymatic interactions
- insensitive to changes in blood flow
