Drug Transporters Flashcards
Major drug transporters
-Efflux
-Uptake
Efflux transporters
-P-glycoprotein
Uptake transporters
-OATP
-PEPT1
P-glycoprotein (P-gp)
-efflux transporter
-affect PERMEABILITY of drugs
-leads to resistance to certain drugs
-aka MDR1
P-gp expressed where
-brain
-liver
-kidney
-testis
-cancer
-apical side of tissue
P-gp in intestinal epithelia
-pumps drug out into intestine
P-gp in hepatocytes
-pumps drug to bile canaliculi
-secreted to bile
-bile goes to intestine
Pgp in kidney prox tubules
-pumps drug to urine
P-gp in blood brain barrier
-pumps drug away from brain into blood
Blood Brain Barrier
-tight junction
-lipophilic molecules can diffuse in
-P-gp pumps out foreign substances
P-gp substrates
-many lipophilic compounds
-Paclitaxel
-anti cancer
-anti HIV
-anti infectives
-CV
Paclitaxel
-P-gp substrate
-does not reach brain in Xray example
P-gp inhibition
more drug in brain
P-Gp in placenta
-part of fetal protection system
-pumps drug back into maternal drug
P-Gp inhibitors will increase drug exposure to
-brain
-fetus
Organic anion transporting protein (OATP)
-300 member family, 11 in humans
-uptake transporters
-pump drug IN
OATP substrates
-bilirubin, bile salts, steroid hormone metabolites
-Fexofenadine, statins
OATP tissue distribution
-liver
-small intestine
OATP1B1 in liver
-pump drug INTO liver
Statins
-need to reach liver to work
-OATP substrates
-myopathy risk
myopathy mech
-OATP1B1 inhibition
-dec statin concentration in liver
-inc statin in plasma
-inc statin myopathy (muscle)
OATP1B1 inhibition
-lower efficacy
-inc side effects (myopathy)
OATP1B1 genetic polymorphisms
-mutation leads to nonfunctional form (V174A)
-inc statin exposure
PEPT1 tissue distribution
-intestine
PEPT1
-uptake transporter
-pumps drug into enterocytes
-inc drug absorption
GrPEFRUIT JUICE
-inhibits intestinal OATP
-dec drug absorption
=lower drug concentration
PEPT1 substrates
-di/tripeptides
-B-lactam antibiotics
PEPT1 clinical use
-improve oral absorption of drugs
