Uptake transporters and clinical relevance

Question 1

What are the two major super families of transporters in the human genome?

Answer 1

ATP-binding Cassettes (ABC)
Solute Carrier (SLC)

Question 2

Where are the most relevant transporters for drug development expressed?

Answer 2

Epithelia of intestine, liver and kidney

Endothelium of BBB

Question 3

What is the role of transporters found in the liver?

Answer 3

Mediate the uptake of drugs from the blood into the hepatocytes
Excretion of drugs into the bile - efflux transporters

Question 4

What is an example of an uptake transporter found in the liver?

Answer 4

OATP1B1

Question 5

What is an example of an efflux transporter found in the liver?

Answer 5

BCRP

Question 6

The human OATP family exists of how many members?

Answer 6

11

Question 7

OATP1B1 contains ____ putative transmembrane domains and a large extracellular loop

Answer 7

12

Question 8

What is the role of OATP transporters?

Answer 8

Mediate the uptake of substrates in an electro-neutral manner - ATP and Na+ independent

Question 9

OATP1B1 and OATP1B3 are exclusively expressed in the _____

Answer 9

liver

Question 10

Which OATP transporter is distributed throughout the whole hepatic lobes and which one is mainly found in the perivenous areas of the liver?

Answer 10

OATP1B1 lobes

OATP1B3 perivenous area

Question 11

OATP substrates are organic cations. True or false?

Answer 11

False - anions

Question 12

Which OATP transporter is involved in the active uptake of glutathione into the hepatocytes?

Answer 12

OATP1B3

Question 13

OATP1B1 is involved in the active uptake of which group of drugs?

Answer 13

Statins

Question 14

Statins are inhibitors of HMG-CoA reductase. They reduce ________ synthesis in the liver

Answer 14

cholesterol

Question 15

The expression of OATP1B1 is the same in all individuals. True or false?

Answer 15

False - expression and activity varies between individuals

Question 16

Individuals with the 52ICC genotype have increased OATP1B1 activity. True or false?

Answer 16

False - reduced activity meaning reduced active uptake of statins and increased risk of adverse drug reactions

Question 17

OATP1B1 causes there to be higher liver exposure of statins compared to plasma. True or false?

Answer 17

True

Question 18

Cyclosporin and ritonavir inhibit OATP1B1. True or false?

Answer 18

True

Question 19

What are the consequences of inhibition of OATP1B1?

Answer 19

Increased plasma concentration of the ‘victim drug’

Increased risk of adverse effects