Absorption Flashcards
Describe the extent of absorption
Bioavailability
Describe the fraction absorbed
Symbol f. The amount of drug that gets across the gut wall and enters the portal vein. Relevant for orally administered drugs
Properties affecting f
Physicochemistry- small unionised drugs well absorbed large ionised low absorption
Metabolism/transport- how well enzymes metabolise the drug, how well the drug can be transported for removal.
Main enzyme involved in drug metabolism
CYP3A4
Main transporter in drug transport
PGP transporter
What is hepatic extraction determined by?
Liver blood flow and the intrinsic clearance (metabolising enzyme capacity) of the drug.
Is the extraction ratio low or high if liver blood flow is low?
It is high as the slower flow means more time for metabolic activity
Describe extraction of ethanol
It is mixed order so extraction of ethanol dependant on saturation. I.e. if you drink quickly you get saturation so higher blood alcohol. If you drink with food absorption of alcohol is slower so
What is the blood flow to the liver
90L/hr
Describe the extraction ratio or First Pass Extraction
The fraction of a drug that enters the extraction organ (liver/kidneys) that is extracted
Formula for calculating the bioavailability of a drug (extent or F)
F= f*(1-ER) Bioavailability = fraction absorbed * (1- extraction ratio)
What is gentamicins clearance and extent (f)
6L/hr (GFR)
5%
What is the extent of simvastatin and why
Around 50% because CYP3A4 metabolizes it in the gut before absorption occurs
What is the extent of digoxin and why
65% due to PGP transporter that transports digoxin out of intestinal cells before absorption occurs
Why is ethanols ER 10-70%
Because ethanol’s clearance is mixed order in that it is relative to concentration. When portal vein concentration is high the liver enzymes are saturated so only 10% of ethanol is removed by liver, when the concentrations are low 70% of ethanol on the portal vein is removed.
