Implications of ABC transporters on the disposition of typical veterinary medicinal products.
The ATP-Binding Cassette (ABC) transporters ABCB1, ABCC2 and ABCG2 are efflux transporters that facilitate the excretion of drugs, contribute to the function of biological barriers and maintain low cytoplasmic substrate concentrations in cells. ABC transporters modulate drug absorption, distribution and elimination according to the level of expression in the intestine, liver, kidney, and at biological barriers such as the blood-brain barrier. Moreover individual transporters are known to convey multi-drug resistance to tumour cells. While these diverse functions have been described in laboratory animal studies and in humans, the available information is very limited in animal species that are typical veterinary patients. This brief review summarizes the available data on organ distribution and expression levels in animals, genetic defects in dogs resulting in a non-functional P-gp expression, and describes examples of kinetic investigations directed to assess the clinical relevance of species differences in ABC-transporter expression.
Schrickx
Jan A
JA
Utrecht University, Faculty of Veterinary Medicine, Veterinary Pharmacology, Pharmacy and Toxicology, Yalelaan 104, 3584 CM Utrecht, Netherlands. j.a.schrickx@uu.nl
Fink-Gremmels
Johanna
J
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D007408:Intestinal Absorption; D008892:Milk / Q000737:chemistry; D000089762:Multidrug Resistance-Associated Protein 2; D009154:Mutation; D013045:Species Specificity; D014018:Tissue Distribution; D019155:Veterinary Drugs / Q000378:metabolism* / Q000493:pharmacokinetics*
C000715087:ABCC2 protein, human; D018528:ATP-Binding Cassette Transporters; D000089762:Multidrug Resistance-Associated Protein 2; D019155:Veterinary Drugs