Transporters: Importance in Drug Absorption, Distribution, and Removal
There is an increasing appreciation of the role that transport proteins play in the absorption, distribution, and elimination of a wide variety of drugs in clinical use. These transporters can be divided into efflux transporters belonging to the ATP-binding cassette (ABC) family and solute carrier (SLC) family members that mediate the influx or bidirectional movement of drugs across the cell membrane. Their coordinated expression and activities at the basolateral and apical side of transporting epithelia are significant determinants of drug disposition, drug–drug interactions, and variability in drug response and toxicity. This chapter focuses on the major SLC and ABC drug transporters expressed in intestine, liver, and kidney, with special emphasis on their distribution, mode of action, and drug substrate specificity.
KeywordsBasolateral Membrane Organic Anion Organic Cation Brush Border Membrane Efflux Transporter
- Bailey PD, Boyd CA, Collier ID, George JP, Kellett GL, Meredith D, Morgan KM, Pettecrew R and Price RA (2006) Affinity prediction for substrates of the peptide transporter PepT1. Chem Commun (Camb)3:323–325.Google Scholar
- Ballatori N (2005) Biology of a novel organic solute and steroid transporter, OSTalpha-OSTbeta. Exp Biol Med (Maywood) 230:689–698.Google Scholar
- Lang T, Hitzl M, Burk O, Mornhinweg E, Keil A, Kerb R, Klein K, Zanger UM, Eichelbaum M and Fromm MF (2004) Genetic polymorphisms in the multidrug resistance-associated protein 3 (ABCC3, MRP3) gene and relationship to its mRNA and protein expression in human liver. Pharmacogenetics 14:155–164.CrossRefPubMedGoogle Scholar
- Smeets PH, van Aubel RA, Wouterse AC, van den Heuvel JJ and Russel FG (2004) Contribution of multidrug resistance protein 2 (MRP2/ABCC2) to the renal excretion of p-aminohippurate (PAH) and identification of MRP4 (ABCC4) as a novel PAH transporter. J Am Soc Nephrol 15:2828–2835.CrossRefPubMedGoogle Scholar
- Zhou K, Donnelly LA, Kimber CH, Donnan PT, Doney AS, Leese G, Hattersley AT, McCarthy MI, Morris AD, Palmer CN and Pearson ER (2009) Reduced function SLC22A1 polymorphisms encoding organic cation transporter 1 (OCT1) and glycaemic response to metformin: a Go-DARTS study. Diabetes: Mar 31. [Epub ahead of print].Google Scholar