Pharmacogenetics of intestinal absorption.
The small intestine is the primary site of absorption for many drugs administered orally and so is the target tissue for pharmacotherapeutic strategies to control the oral absorption of drugs. Drug transporters, including the ATP-binding cassette (ABC) superfamily and the solute carrier (SLC) superfamily, have been considered to play a physiological role in regulating the absorption of xenobiotics, and variations in their expression level and function in the small intestine cause intra- and inter-individual variation in the oral absorption of drugs. Recent advances in molecular biology have suggested that genetic polymorphisms are associated with the expression level and function, and thereby inter-individual variation. In this review, the pharmacogenetics of these transporters is summarized, and their future significance in the clinical setting is discussed.
Nakamura
Tsutomu
T
Department of Clinical Evaluation of Pharmacotherapy, Kobe University Graduate School of Medicine, 1-5-6, Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. tsutomun@med.kobe-u.ac.jp
Yamamori
Motohiro
M
Sakaeda
Toshiyuki
T
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D005838:Genotype; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects* / Q000235:genetics*; D007422:Intestines / Q000201:enzymology; D027381:Liver-Specific Organic Anion Transporter 1; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D027361:Organic Anion Transporters / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000378:metabolism; D000074011:Peptide Transporter 1; D010597:Pharmacogenetics; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters / Q000378:metabolism
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D027381:Liver-Specific Organic Anion Transporter 1; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D000074011:Peptide Transporter 1; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters; C116614:ABCG2 protein, human; C492020:SLC22A5 protein, human; C503999:SLCO1B1 protein, human