Organic Anion And Cationn Transporters

Question 1

Why are OATs and OCTs so important in drug distribution?

Answer 1

Many drugs are hydrophilic (charged).
For drugs to reach their target, carriers are required at each membrane boundary from site of administration
Tissue distribution of drugs depends upon expression profiles of carriers
OAT/OCT expression profiles can influence drug side effects and toxicity

Question 2

What is the role of kidney OAT/OCT in drug elimination

Answer 2

OAT/OCT drug transport in kidney shortens half-life (e.g. penicillin)
Many drugs are modified in the liver and become more charged - more likely to be eliminated in kidney.
Competition of drugs for OCT/OATs in kidney can influence elimination kinetics - e.g. probenecid used to extend half life of penicillin

Question 3

Why does cisplatin cause kidney damage?

Answer 3

It is a good OCT2 substrate but a poor MATE1 or MATE2-K substrate, so accumulates in proximal tubule cells -> kidney damage