ADME 3

Question 1

What are the three sites of drug excretion?

Answer 1

kidney, biliary excretion (MW>400 where 177 is addd to the MW of the drug via glucoronides) and lungs i.e. anaesthetic gases

Question 2

How does entero hepatic circulation work?

Answer 2

Drug entering the liver via the portal vein or hepatic artery may be glucuronidated. This metabolite may then be exported to the intestines via the bile duct. bile is there to make things easily absorbed. Large physical chemical property drug can be reabsorbed as a result when in bile. β-glucuronidase (from gut microflora) may then remove the glucuronide portion of the metabolite ,reforming the original drug, which may be absorbed to start the process again.

Question 3

What is the effect of enterohepatic recirculation on plasma concentration after single oral dose?

Answer 3

When you start your meal, your gall bladder releases bile with the drug which means it enters the enterohepatic recirculation and so gains a prolonged half life.

Question 4

In humans what must be the mw of a drug to switch the excretion route from urine to faeces?

Answer 4

400-500 MW in humans. This suggests the importance of the urinary excretion route.
200 MW in rats
188 is 50% excretion in both routes for rats.

Question 5

What are the three processes of renal excretion?

Answer 5

glomerulus filtration
Active secretion
Filtrate

Question 6

How does glomerular filtration work?

Answer 6

1. Glomerular filtration of unbound drug, rate (GFR) 130 mL/min in healthy adult, 10% renal
   blood flow

Question 7

How does active secretion work?

Answer 7

2. Active secretion of both free and protein bound drug by transporters:Anions: urate, penicillin, glucuronide & sulphate conjugates Cations: choline, histamine, basic drugs,eg amines

Question 8

How does filtration work?

Answer 8

3. Filtrate 100-fold concentrated in tubules for a

favourable conc gradient for reabsorption by passive diffusion