Transporters - Gerk Study Guide

• P-gp, BCRP, OATP1B1/1B3

Most transporter DDI’s occur where

reabsorption

PEPT transporter works by

Efflux (pushing out of the blood); exception in the brain (pGp pumps into the blood)

PgP transporter works by ____, with exception of

Helping drugs into liver

OAT works by 

•  use ATP directly to pump drugs against the concentration gradient

What do ABC transports do?

• PgP

• BCRP

• BSEP

• MRP

Examples of ABC transporters

• Expression: BBB, liver, kidney, intestine, placenta

• Substrates: chemo drugs, HIV protease inhibitors, CCBs, etc

• Inhibitors: macrolides, ketoconazole, HIV-PIs

Inducers: PXR

• GI Tract

  • Effect: delays/limits absorption and enhances gut metabolism

  • ↓ F oral → pumps it out and ↑ exposure to enzymes

    • Inhibit P-gp → ↑ F

• Brain

  • Pumps drugs AWAY from BRAIN into blood stream 

PgP information regarding induction, inhibition, and substrates

• plasma membrane proteins expressed in many barrier epithelia that indirectly use cellular energy to facilitate diffusion or active transport of organic anions/cations

Solute Carrier Transporters are

“OATS go with the “FLOW” in the LIVER”

Pneumonic to remember SLC transporters

OATPS // PEPTs // OATs + OCTs

SLC transporters

• Inhibitors: rifampin, HIV-PIs

• Inducers: rifampin (PXR)

  • Net effect w/ rifampin depends on Km

    • ↓ Km (high affinity) substrate ~ ↑ activity

    • ↑ Km (low affinity) substrate ~ ↓ activity

OATP’s inducers and inhibitors

Statins! 

SLC’s most important substrates