What is the process by which a drug is transported by the bloodstream to receptor sites?

  • Alvarado F, Van Os CH (1986) (eds) Ion gradient-coupled transport. Elsevier Science Publishers, Amsterdam, pp 442

    Google Scholar 

  • Atanasova S, von Ahsen N, Dimitrov T, Armstrong V, Oellerich M, Toncheva D (2004) MDR1 haplotypes modify BEN disease risk: a study in Bulgarian patients with Balkan endemic nephropathy compared to healthy controls. Nephron Exp Nephrol 96:7–13

    Google Scholar 

  • Athayde AL, Ivory CF (1985) Electrical pumping in carrier-mediated membrane transport. J Membr Sci 24:309–323

    CAS  Google Scholar 

  • Ayrton A, Morgan P (2001) Role of transport proteins in drug absorption, distribution and excretion. Xenobiotica 31:469–497

    PubMed  CAS  Google Scholar 

  • Bilej M, Vetvicka V (1989) The transmembrane and intracellular transport of drugs: interactions with the cytosceletal network. Crit Rev Ther Drug Carrier Syst 6:613–691

    PubMed  CAS  Google Scholar 

  • Bolhuis H, van Veen HW, Poolman B, Driessen AJ, Konings WN (1997) Mechanisms of multidrug transporters. FEMS Microbiol Rev 21:55–84

    PubMed  CAS  Google Scholar 

  • Borst P, Oude Elferink R (2002) Mammalian ABC transporters in health and disease. Annu Rev Biochem 71:537–592

    PubMed  CAS  Google Scholar 

  • Brant SR, Panhuysen CI, Nicolae D, Reddy DM, Bonen DK, Karaliukas R, Zhang L, Swanson E, Datta LW, Moran T, Ravenhill G, Duerr RH, Achkar JP, Karban AS, Cho JH (2003) MDR1 Ala893 polymorphism is associated with inflammatory bowel disease. Am J Hum Genet 73:1282–1292

    PubMed  CAS  Google Scholar 

  • Brodie BB (1964) Physico-chemical factors in drug absorption. In: Binns TB (ed) Absorption and distribution of drugs. Livingstone, Edinburgh, pp 16–48

    Google Scholar 

  • Brodie BB, Hogben CAM (1957) Some physico-chemical factors in drug action. J Pharmacy Pharmacol 9:345–380

    CAS  Google Scholar 

  • Burckhardt BC, Burckhardt G (2003) Transport of organic anions across the basolateral membrane of proximal tubule cells. Rev Physiol Biochem Pharmacol 146:95–158

    PubMed  CAS  Google Scholar 

  • Burckhardt G, Wolff NA (2000) Structure of renal organic anion and cation transporters. Am J Physiol Renal Physiol 278:F853–F866

    PubMed  CAS  Google Scholar 

  • Caldwell PC (1956) The effects of certain metabolic inhibitors on the phosphate esters of the squid giant axon. J Physiol (London) 132:35

    CAS  Google Scholar 

  • Caldwell PC (1960) The phosphorus metabolism of squid axons and its relationship to the active transport of sodium. J Physiol (London) 152:545–560

    CAS  Google Scholar 

  • Carafoli E, Scarpa A (1982) (eds) Transport-ATPases. Ann N Y Acad Sci, New York (402):604

    Google Scholar 

  • Catania VA, Sanchez Pozzi EJ, Luquita MG, Ruiz ML, Villanueva SS, Jones B, Mottino AD (2004) Co-regulation of expression of phase II metabolizing enzymes and multidrug resistance-associated protein 2. Ann Hepatol 3:11–17

    PubMed  Google Scholar 

  • Chan LMS, Lowes S, Hirst BH (2004) The ABCs of drug transport in intestine and liver: efflux proteins limiting drug absorption and bioavailability. Eur J Pharmaceut Sci 21:25–51

    CAS  Google Scholar 

  • Chandra P, Brouwer KL (2004) The complexities of hepatic drug transport: current knowledge and emerging concepts. Pharm Res 21:719–735

    PubMed  CAS  Google Scholar 

  • Crane RK, Krane SM (1959) Studies on the mechanism of intestinal active transport of sugars. Biochim Biophys Acta 31:397–401

    PubMed  CAS  Google Scholar 

  • Dahlquist R, Ejvinsson G, Schenk-Gustaffson K (1980) Effect of quinidine on plasma concentration and renal clearance of digoxin. A clinically important drug interaction. Brit J Clin Pharmacol 9:413–418

    Google Scholar 

  • Daniel H (2004) Molecular and integrative physiology of intestinal peptide transport. Annu Rev Physiol 66:361–384

    PubMed  CAS  Google Scholar 

  • Daniel H, Rubio-Aliaga I (2003) An update on renal peptide transporters. Am J Physiol Renal Physiol 284:F885–F892

    PubMed  CAS  Google Scholar 

  • Dean M, Rzhetsky A, Allikmets R (2001) The human ATP-binding cassette (ABC) transporter superfamily. Genome Res 11:1156–1166

    PubMed  CAS  Google Scholar 

  • Delgoda R, Westlake AC (2004) Herbal interactions involving cytochrome p450 enzymes: a mini review. Toxicol Rev 23:239–249

    PubMed  CAS  Google Scholar 

  • DeVree J, Jacquemin E, Sturm E, Creteil D, Bosma PJ, Aten J, DeLeuze JF, Desrochers M, Burdelski M, Bernard O, Oude Elferink RP, Hadchouel M (1998) Mutations in the MDR3 gene cause progessive familial intahepatic cholestasis. Proc Natl Acad Sci USA 95:282–287

    CAS  Google Scholar 

  • Diamond JM,Wright EM (1969) Biological membranes: the physical basis of ion and nonelectrolyte selectivity. Annu Rev Physiol 31:581–646

    PubMed  CAS  Google Scholar 

  • Dietrich CG, Geier A, Oude Elferink RPJ (2003) ABC or oral bioavailability: transporters as gatekeepers in the gut. Gut 52:1788–1795

    PubMed  CAS  Google Scholar 

  • Doering W (1979) Quinidine-digoxin interaction: Pharmacokinetics, underlying mechanism and clinical implications. N Engl J Med 301:400–404

    Article  PubMed  CAS  Google Scholar 

  • Donner MG, Keppler D (2001) Up-regulation of basolateral multidrug resistance protein 3 (Mrp3) in cholestatic rat liver. Hepatology 34:351–359

    PubMed  CAS  Google Scholar 

  • Drescher S, Schaeffeler E, Hitzl M, Hofmann U, Schwab M, Brinkmann U, Eichelbaum M, Fromm MF (2002) MDR1 gene polymorphisms and disposition of the P-glycoprotein substrate fexofenadine. Br J Clin Pharmacol 53:526–534

    PubMed  CAS  Google Scholar 

  • Drescher S, Glaser H, Mürdter T, Hitzl M, Eichelbaum M, Fromm MF (2003) P-glycoprotein-mediated intestinal and biliary digoxin transport in humans. Clin Pharmacol Ther 73:223–231

    PubMed  CAS  Google Scholar 

  • Dresser MJ, Leabman MK, Giacomini KM (2001) Transporters involved in the elimination of drugs in the kidney: organic anion transporters and organic cation transporters. Pharmaceut Sci 90:397–420

    CAS  Google Scholar 

  • Dresser GK, Bailey DG, Leake BF, Schwarz UI, Dawson PA, Freeman DJ, Kim RB (2002) Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake to decrease the oral availability of fexofenadine. Clin Pharmacol Ther 71:11–20

    PubMed  CAS  Google Scholar 

  • Drozdzik M, Bialecka M, Mysliwiec K, Honczarenko K, Stankiewicz J, Sych Z (2003) Polymorphism in the P-glycoprotein drug transporter MDR1 gene: a possible link between environmental and genetic factors in Parkinson’s disease. Pharmacogenetics 13:259–263

    PubMed  CAS  Google Scholar 

  • Elleroy JC, Lew VL (1977) (eds) Membrane transport in red cells. Academic Press, New York, pp 469

    Google Scholar 

  • Fardel O, Jigorel E, Le Vee M, Payen L (2005) Physiological, pharmacological and clinical features of the multidrug resistance protein 2. Biomed Pharmacother 59:104–114

    PubMed  CAS  Google Scholar 

  • Fehrenbach T, Cui Y, Faulstich H, Keppler D (2003) Characterization of the transport of the bicyclic peptide phalloidin by human hepatic transport proteins. Naunyn-Schmiedeberg’s Arch Pharmacol 368:415–420

    CAS  Google Scholar 

  • Fromm MF (2004) Importance of P-glycoprotein at blood-tissue barriers. Trends Pharmacol Sci 25:423–429

    PubMed  CAS  Google Scholar 

  • Fromm MF, Kim RB, Stein CM, Wilkinson GR, Roden DM (1999) Inhibition of P-glycoprotein-mediated drug transport: a unifying mechanism to explain the interaction between digoxin and quinidine. Circulation 99:552–557

    PubMed  CAS  Google Scholar 

  • Gao B, St Pierre MV, Stieger B, Meier PJ (2004) Differential expression of bile salt and organic anion transporters in developing rat liver. J Hepatol 41:202–208

    Google Scholar 

  • Gerok W, Sickinger K (1973) (eds) Drugs and the liver. Schattauer Verlag, Stuttgart, pp 441

    Google Scholar 

  • Geyer J, Döring B, Godoy JR, Moritz A, Petzinger E (2005a) Development of a PCR-based diagnostic test detecting a nt230(del4) MDR1 mutation in dogs: verification in a moxidectin-sensitive Australian Shepherd. J Vet Pharmacol Ther 28:95–99

    PubMed  CAS  Google Scholar 

  • Geyer J, Döring B, Godoy JR, Moritz A, Petzinger E (2005b) Frequency of the nt230(del4) MDR1 mutation in Collies and related dog breeds from Germany. J Vet Pharmacol Ther 28:545–551

    PubMed  CAS  Google Scholar 

  • Geyer J, Wilke T, Petzinger E (2006) The solute carrier family SLC10: more than a family of bile acid transporters regarding function and phylogenetic relationships. Naunyn-Schmiedeberg’s Arch Pharmacol, this issue

  • Gilles-Baillieu M, Gilles R (1983) (eds) Intestinal transport: fundamental and comparative aspects. Springer-Verlag, Berlin Heidelberg New York, pp 375

    Google Scholar 

  • Gillette JR (1963) Metabolism of drugs and other foreign compounds by enzymatic mechanisms. Progr Drug Res 6:11–75

    CAS  Google Scholar 

  • Grammatté T, Oertel R (1999) Intestinal secretion of intravenous talinolol is inhibited by luminal R-verapamil. Clin Pharmacol Ther 66:239–245

    Google Scholar 

  • Grammatté T, Oertel R, Terhaa, B, Kirch W (1996) Direct demonstration of small intestinal secretion and side-dependent absorption of the β-blocker talinolol in human. Clin Pharmacol Ther 59:541–549

    Google Scholar 

  • Greiner B, Eichelbaum M, Fritz P, Kreichgauer HP, von Richter O, Zundler J, Kroemer HK (1999) The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. J Clin Invest 104:147–153

    PubMed  CAS  Google Scholar 

  • Greger R, Lang F, Silbernagl S (1981) (eds) Renal transport of organic substances. Springer-Verlag, Berlin Heidelberg New York, pp 314

    Google Scholar 

  • Gründemann D, Gorboulev V, Gambaryan S, Veyhl M, Koepsell H (1994) Drug excretion mediated by a new prototype of polyspecific transporter. Nature 372:549–552

    PubMed  Google Scholar 

  • Habig WH, Pabst MJ, Fleischner G, Gatmaitan Z, Arias IM, Jacobvy WB (1974) The identity of glutathione S-transferase B with ligandin, a major binding protein of liver. Proc Natl Acad Sci USA 71:3879–3882

    PubMed  CAS  Google Scholar 

  • Hagenbuch B, Meier PJ (2003) The superfamily of organic anion transporting polypeptides. Biochim Biophys Acta 1609:1–18

    PubMed  CAS  Google Scholar 

  • Haimeur A, Conseil G, Geeley RG, Cole SP (2004) The MRP-related and BCRP/ABCG2 multidrug resitance proteins: biology, substrate specificity and regulation. Curr Drug Metab 5:21–53

    PubMed  CAS  Google Scholar 

  • Hediger MA, Coady MJ, Ikeda TS, Wright EM (1987) Expression cloning and cDNA sequencing of the Na+/glucose cotransporter. Nature (London) 330:379–381

    CAS  Google Scholar 

  • Hediger MA, Romero MF, Peng JB, Rolfs A, Takanaga H, Bruford EA (2004) The ABCs of solute carriers: physiological, pathological, and therapeutic implications of human membrane transport proteins. Pfluegers Arch 447:465–468

    CAS  Google Scholar 

  • Heinz E (1972) (eds) Na-linked transport of organic solutes. The coupling between electrolyte and nonelectrolyte transport in cells. Springer-Verlag, Berlin Heidelberg New York, pp 201

    Google Scholar 

  • Heinz E (1978) (eds) Mechanics and energetics of biological transport. Springer-Verlag, Berlin Heidelberg New York, pp 159

    Google Scholar 

  • Hoffmann U, Kroemer HK (2004) The ABC transporters MDR1 and MRP2: multiple functions in disposition of xenobiotics and drug resistance. Drug Metab Rev 86:669–701

    Google Scholar 

  • Hoffmeyer S, Burk O, von Richter O, Arnold H P, Brockmöller J, Johne A, Cascorbi I, Gerloff T, Roots I, Eichelbaum M, Brinkmann U (2000) Functional polymorphisms of the human multidrug-resitance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Nat Acad Sci U S A 97:3473–3478

    CAS  Google Scholar 

  • Hogben CAM, Tocco DJ, Brodie BB, Schanker LS (1959) On the mechanism of intestinal drug absorption of drugs. J Pharmacol Exp Ther 125:275–282

    PubMed  CAS  Google Scholar 

  • Homolya L, Varadi A, Sarkadi B (2003) Multidrug resitance-assiciated proteins: export pumps for conjugates with glutathione, glucuronate or sulfate. Biofactors 17:103–114

    PubMed  CAS  Google Scholar 

  • Hsiang B, Zhu Y, Wang Z, Wu Y, Sasseville V, Yang WP, Kirchgessner TG (1999) A novel human hepatic organic anion transporting polypeptide (OATP2) Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J Biol Chem 274:37161–37168

    PubMed  CAS  Google Scholar 

  • Ieiri I, Takane H, Otsubo K (2004) The MDR1 (ABCB1) gene polymorphism and its clinical implications. Clin Pharmacokinet 43:553–576

    PubMed  CAS  Google Scholar 

  • Iida A, Saito S, Sekine A, Mishima C, Kondo K, Kitamura Y, Harigae S, Osawa S, Nakamura Y (2001) Catalog of 258 single-nucleotide polymorphisms (SNPs) in genes encoding three organic anion transporters, three organic anion transporting polypeptides, and three NADH : ubichinone oxidoreductase flavoproteins. J Hum Genet 46:668–683

    PubMed  CAS  Google Scholar 

  • Ito K, Iwatsuro T, Kanamitsu S, Ueda K, Suzuki H, Sugiyama Y (1998) Prediction of pharmacokinetic alterations caused by drug-drug interactions: metabolic interaction in the liver. Pharmacol Rev 50:387–411

    PubMed  CAS  Google Scholar 

  • Jackson MJ (1987) Drug transport across gastrointestinal epithelia. In: LR Johnson (ed) Physiology of the gastrointestinal tract. Raven Press, New York, pp 1597–1621

    Google Scholar 

  • Jacquemin E, Hagenbuch B, Stieger B, Wolkoff AW, Meier PJ (1994) Expression cloning of a rat liver Na(+)-independent organic anion transporter. Proc Natl Acad Sci USA 91:133–137

    PubMed  CAS  Google Scholar 

  • Juliano RL, Ling V (1976) A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 455:152–162

    PubMed  CAS  Google Scholar 

  • Jansen PLM (2001) Hereditary defects of hepatobiliary transport. In: Matern S, Boyer JL, Keppler D, Meier-Abt PJ (eds) Hepatobiliary transport: from bench to bedside. Kluwer Acad. Publ., Dordrecht, pp 91–97

    Google Scholar 

  • Kafka A, Sauer G, Jaeger C, Grundmann R, Kreienberg R, Zeillinger R, Deissler H (2003) Polymorphism C3435T of the MDR-1 gene predicts response to preoperative chemotherapy in locally advanced breast cancer. Int J Oncol 22:1117–1121

    PubMed  CAS  Google Scholar 

  • Keynes RD (1961) The energy source for active transport in nerve and muscle. In: A Kleinzeller, A Kotyk (eds) Membrane transport and metabolism. Academic Press, London, pp 131–139

    Google Scholar 

  • Kilby JM, Hill A, Buss N (2002) The effect of ritonavir on saquinavir plasma concentration is independent of ritonavir dosage: combined analysis of pharmacokinetic data from 97 subjects. HIV Med 3:97–104

    PubMed  CAS  Google Scholar 

  • Kim RB (2004) 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) and genetic variability (single nucleotide polymorphisms) in a hepatic drug uptake transporter: what’s it all about? Clin Pharmacol Ther 75:381–385

    PubMed  CAS  Google Scholar 

  • Kim RB, Fromm MF, Wandel C, Leake B, Wood AJJ, Roden DM, Wilkinson GR (1998) The drug transporter p-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Invest 101:289–294

    PubMed  CAS  Google Scholar 

  • Klaassen CD, Watkins JB (1984) Mechanisms of bile formation, hepatic uptake, and biliary excretion. Pharmacol Rev 36:1–67

    PubMed  CAS  Google Scholar 

  • Koepsell H, Endou H (2004) The SLC22 drug transporter family. Pflügers Arch 447:666–676

    PubMed  CAS  Google Scholar 

  • König J, Rost D, Cui Y, Keppler D (1999) Characterisation of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrane. Hepatology 29:1156–1163

    PubMed  Google Scholar 

  • König J, Seithel A, Gradhand U, Fromm MF (2006) Pharmacogenomics of human OATP transporters. Naunyn-Schmiedeberg’s Arch Pharmacol, this issue

  • Kramer M, Lauterbach F (1977) (eds) Intestinal permeation. Excerpta Medica, Amsterdam, pp 449

    Google Scholar 

  • Kramer W, Wess G (1996) Bile acid transport systems as pharmaceutical targets. Eur J Clin Invest 26:715–732

    PubMed  CAS  Google Scholar 

  • Kramer W, Wess G, Schubert G, Bickel M, Girbig F, Gutjahr U, Kowalewski S, Baringshaus K-H, Ehnsen A, Glombik H, Müllner S, Neckermann G, Schulz S, Petzinger E (1992) Liver-specific drug trageting by coupling with bile acids. J Biol Chem 267:18598–18604

    PubMed  CAS  Google Scholar 

  • Kramer W, Sauber K, Baringhaus K-H, Kurz M, Stengelin S, Lange G, Corsiero D, Girbig F, König W, Weyland C (2001) Identification of the bile acid-binding site of the ileal lipid-binding protein by photoaffinty labelling, matrix-assisted laser desorption ionization-mass spectrometry, and NMR structure. J Biol Chem 276:7291–7301

    PubMed  CAS  Google Scholar 

  • Krusekopf S, Roots I (2005) St. John’s wort and its constituent hyperforin concordantly regulate expression of genes encoding enzymes involved in basic cellular pathways. Pharmacogenetics 15:817–829, Genomics

    CAS  Google Scholar 

  • Kubitz R, Keitel V, Häussinger D (2005) Inborn errors of biliary canalicular transport systems. Meth Enzymol 400:558–569

    PubMed  CAS  Google Scholar 

  • Kullak-Ublick GA, Beuers U, Paumgartner G (2000) Hepatobiliary transport. J Hepatol 32:3–18

    PubMed  CAS  Google Scholar 

  • Kullak-Ublick GA, Stieger B, Meier PJ (2004) Enterohepatic bile salt transporters in normal physiology and liver disease. Gastroenterology 126:322–342

    PubMed  CAS  Google Scholar 

  • LeFevre PG (1948) Evidence of active transfer of certain non-electrolytes across the human red cell membrane. J Gen Physiol 31:505–507

    CAS  PubMed  Google Scholar 

  • LeFevre PG (1975) The present state of the carrier hypothesis. In: Bronner F, Kleinzeller A (eds) Current topics in membranes and transport. Academic Press, London, pp 109–215

    Google Scholar 

  • Leslie EM, Deeley RG, Cole SP (2001) Toxicological relevance of the multidrug resistance protein 1, MRP1 (ABCC1) and related transportes. Toxicology 167:3–23

    PubMed  CAS  Google Scholar 

  • Leslie EM, Deeley RG, Cole SP (2005) Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2 and BCRP (ABCG2) in tissue defense. Toxicol Appl Pharmacol 204:216–237

    PubMed  CAS  Google Scholar 

  • Levi AJ, Gatmaitan Z, Arias IM (1969) Two hepatic cytoplasmic protein fractions, Y and Z, and their possible role in the hepatic uptake of bilirubin, sulfobromophthalein, and other anions. J Clin Invest 48:2156–2167

    PubMed  CAS  Google Scholar 

  • Liu L, Pang KS (2005) The roles of transporters and enzymes in hepatic drug processing. Drug Metab Dispos 33:1–9

    PubMed  Google Scholar 

  • Lloyd JB (2000) Lysosome membrane permeability: implications for drug delivery. Adv Drug Deliv Rev 41:189–200

    PubMed  CAS  Google Scholar 

  • Maisonnette F, Abita T, Barriere E, Pichon N, Vincensini JF, Descottes B (2005) The MDR3 gene mutation: a rare cause of progressive familial intrahepatic cholestasis (PFIC). Ann Chir 130:581–583

    PubMed  CAS  Google Scholar 

  • Mannel M (2004) Drug interactions with St John’s wort: mechanisms and clinical implications. Drug Saf 27:773–797

    PubMed  CAS  Google Scholar 

  • Mealey KL, Bentjen SA, Gay JM, Cantor GH (2001) Ivermectin sensitivity in collies is associated with a deletion mutation in the mdr1 gene. Pharmacogenetics 11:727–733

    PubMed  CAS  Google Scholar 

  • Meijer DK (1993) Drug targeting to the liver with bile acids: the “Trojan horse” resurrected? Hepatology 17:945–948

    PubMed  CAS  Google Scholar 

  • Milne RW, Larsen LA, Jorgensen KL, Bastlund JF, Stretch GL, Evans AM (2000) Hepatic disposition of fexofenadine: influence of the transport inhibitors erythromycin and dibromosulphothalein. Pharmaceutical Res 17:1511–1515

    CAS  Google Scholar 

  • Mizuno N, Niwa T, Yotsumoto Y, Sugiyama Y (2003) Impact of drug transporter studies on drug discovery and development. Pharmacol Rev 55:425–461

    PubMed  CAS  Google Scholar 

  • Müller M, Jansen PLM (1998) The secretory step of the liver: new aspects of hepatobiliary transport. J Hepatol 28:344–354

    PubMed  Google Scholar 

  • Murray JW, Wolkoff AW (2003) Roles of the cytoskeleton and motor proteins in endocytic sorting. Adv Drug Deliv Rev 55:1385–1403

    PubMed  CAS  Google Scholar 

  • Niemi M, Schaeffeler E, Lang T, Fromm MF, Neuvonen M, Kyrklund C, Backman J T, Kerb R, Schwab M, Neuvonen PJ, Eichelbaum M, Kivistö KJ (2004) High plasma pravastatin concentrations are associated with single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide-C (OATP-C, SCLO1B1). Pharmacogenetics 14:429–440

    PubMed  CAS  Google Scholar 

  • Niemi M, Neuvonen PJ, Hofmann U, Backman JT, Schwab M, Lütjohann D, von Bergmann K, Eichelbaum M, Kivistö KT (2005a) Acute effects of pravastatin on cholesterol synthesis are associated with SCLO1B1 (encoding OATP1B1) haplotype *17. Pharmacogen Genom 15:303–309

    Article  CAS  Google Scholar 

  • Niemi M, Kivistö KT, Hofmann U, Schwab M, Eichelbaum M, Fromm M (2005b) Fexofenadine pharmacokinetics are associated with a polymorphism of the SCLO1B1 gene (encoding OATP1B1). Br J Clin Pharmacol 59:602–604

    PubMed  CAS  Google Scholar 

  • Nozawa T, Nakajima M, Tamai I, Noda K, Nezu JI, Sai Y, Tsuji A, Yokoi T (2002) Genetic polymorphisms of human organic anion transporters OATP-C (SLC21A6) and OATP-B (SLC21A9): allele frequencies in the Japanese population and functional studies. J Pharmacol Exp Ther 302:804–813

    PubMed  CAS  Google Scholar 

  • Ogawa K, Suzuki H, Hirohashi T, Ishikawa T, Meier PJ, Hirose K, Akizawa T, Yoshioka M, Sugiyama Y (2000) Characterization of inducible nature of MRP3 in rat liver. Am J Physiol Gastrointest Liver Physiol 278:G438–G446

    PubMed  CAS  Google Scholar 

  • Ohashi M, Sano N, Takikawa H (2002) Effects of phalloidin on the biliary excretion of cholephilic compounds in rats. Pharmacology 66:31–35

    PubMed  CAS  Google Scholar 

  • Paul AJ, Tranquilli WJ, Seward RL, Todd KS, DiPietro JA (1987) Clinical observations in collies given ivermectin orally. Am J Vet Res 48:684–685

    PubMed  CAS  Google Scholar 

  • Pauli-Magnus C, Meier PJ (2004) Pharmacogenetics of hepatocellular transporters. Pharmacogenetics 13:189–198

    Google Scholar 

  • Paulusma LC, Oude Elferink RP (1997) The canalicular multispecific anion transporter and conjugated hyperbilirubinemia in rat and man. J Mol Med 75:420–428

    PubMed  CAS  Google Scholar 

  • Pedersen KE, Christansen BD, Klittgaard NA, Nielsen-Kudsk F (1983) Effect of quinidine of digoxin bioavailability. Eur J Clin Pharmacol 24:41–47

    PubMed  CAS  Google Scholar 

  • Petzinger E (1981) Competitive inhibition of the uptake of demethylphalloin by cholic acid in isolated hepatocytes. Evidence for a transport competition rather than a binding competition. Naunyn-Schmiedeberg’s Arch Pharmacol 316:345–349

    CAS  Google Scholar 

  • Petzinger E (1994) Transport of organic anions in the liver. An update on bile acid, fatty acid, monocarboxylate, anionic amino acid, cholephilic organic anion, and anionic drug transport. Rev Physiol Biochem Pharmacol 123:47–211

    Article  PubMed  CAS  Google Scholar 

  • Petzinger E, Ziegler K, Frimmer M (1979) Inhibition of 3H-demethylphalloin uptake in isolated rat hepatocytes under various experimental conditions. Naunyn-Schmiedeberg’s Arch Pharmacol 307:275–281

    CAS  Google Scholar 

  • Petzinger E, Kinne RKH, Sies H (1989) (eds) Hepatic transport of organic substances. Springer-Verlag, Berlin Heidelberg New York, pp 435

    Google Scholar 

  • Petzinger E, Nickau L, Horz JA, Schulz S, Wess G, Ehnsen A, Falk E, Baringhaus K-H, Glombik H, Hoffmann A, Müllner S, Nekermann G, Kramer W (1995) Hepatobiliary transport of hepatic 3-hydroxy-3-methylglutaryl Coenzyme A reductase inhibitors conjugated with bile acids. Hepatology 22:1801–1811

    PubMed  CAS  Google Scholar 

  • Pritchard JB, Miller DS (1993) Mechanisms mediating renal secretion of organic anions and cations. Physiol Rev 73:765–796

    PubMed  CAS  Google Scholar 

  • Pulliam JD, Seward RL, Henry RT, Steinberg SA (1985) Investigating ivermectin toxicity in Collies. Vet Med 80:33–40

    Google Scholar 

  • Roninson IB, Chin JE, Choi KG, Gros P, Housman DE, Fojo A, Shen DW, Gottesman MM, Pastan I (1986) Isolation of human mdr DNA sequences amplified in multidrug resistant KB carcinoma cells. Proc Natl Acad Sci U S A 83:4538–4542

    PubMed  CAS  Google Scholar 

  • Rosenberg T, Wilbrandt W (1957) Uphill transport induced by counterflow. J Gen Physiol 41:289–296

    PubMed  CAS  Google Scholar 

  • Rost D, Kartenbeck J, Keppler D (1999) Changes in the localization of the rat canalicular conjugate export pump Mrp2 in phalloidin-induced cholestasis. Hepatology 29:814–821

    PubMed  CAS  Google Scholar 

  • Roulet A, Puel O, Gesta S, Lepage JF, Drag M, Soll M, Alvinerie M, Pineau T (2003) MDR1-deficient genotype in Collie dogs hypersensitive to the P-glycoprotein substrate ivermectin. Eur J Pharmacol 460:85–91

    PubMed  CAS  Google Scholar 

  • Russel FG, Masereeuw R, Van Aubel RA (2002) Molecular aspects of renal anionic drug transport. Annu Rev Physiol 64:563–594

    PubMed  CAS  Google Scholar 

  • Scheffer GL, Kool M, de Haas M, de Vree JM, Pijnenborg AC, Bosman DK, Oude Elferink R, Van Borst P, Scheper RJ (2002) Tissue distribution and induction of human multidrug resistant protein 3. Lab Invest 82:193–201

    PubMed  CAS  Google Scholar 

  • Schwab M, Schaeffeler E, Marx C, Fromm MF, Kaskas B, Metzler J, Stange E, Herfarth H, Schoelmerich J, Gregor M, Walker S, Cascorbi I, Roots I, Brinkmann U, Zanger UM, Eichelbaum M (2003) Association between the C3435T MDR1 gene polymorphism and susceptibility for ulcerative colitis. Gastroenterology 124:26–33

    PubMed  CAS  Google Scholar 

  • Sekine T, Watanabe N, Hosoyamada M, Kanai Y, Endou H (1997) Expression cloning and characterization of a novel multispecific organic anion transporter. J Biol Chem 272:18526–18529

    PubMed  CAS  Google Scholar 

  • Semenza G, Kinne R (1985) (eds) Membrane transport driven by ion gradients. Ann N Y Acad Sci 456:459

  • Shibayama Y, Ikeda R, Motoya T, Yamada K (2004) St John’s Wort (Hypericum perforatum) induces overexpression of multidrug resistance protein2 (MRP2) in rats: a 30-day ingestion study. Food Chem Toxicol 42:995–1002

    PubMed  CAS  Google Scholar 

  • Shoda J, Kano M, Oda K, Kamiya J, Nimura Y, Suzuki H, Sugiyama Y, Miyazaki H, Todoroki T, Stengelin S, Kramer W, Matsuzaki Y, Tanaka N (2001) The expression levels of plasma membrane transporters in the cholestatic liver of patients undergoing biliary drainage and their association with the impairment of biliary secretory function. Am J Gastroenterol 96:3368–3378

    PubMed  CAS  Google Scholar 

  • Siegsmund M, Brinkmann U, Schaffeler E, Weirich G, Schwab M, Eichelbaum M, Fritz P, Burk O, Decker J, Alken P, Rothenpieler U, Kerb R, Hoffmeyer S, Brauch H (2002) Association of the P-glycoprotein transporter MDR1(C3435T) polymorphism with the susceptibility to renal epithelial tumors. J Am Soc Nephrol 13:1847–1854

    PubMed  CAS  Google Scholar 

  • Smith JN, Williams RT (1949) The metabolism of phenacetin (p-ethoxyacetanilide) in the rabbit and a further observation on acetanilide metabolism. Biochem J 44:239–242

    CAS  Google Scholar 

  • Soroka CJ, Lee JM, Azzaroli F, Boyer JL (2001) Cellular localization and up-regulation of multidrug resistance-associated protein 3 in hepatocytes and cholangiocytes during obstructive cholestasis in rat liver. Hepatology 33:783–791

    PubMed  CAS  Google Scholar 

  • Spahn-Langguth H, Baktir G, Radschuweit A, Okyar A, Terhaag B, Ader P, Hanafy A, Langguth P (1998) P-glycoprotein transporters and the gastrointestinal tract: evaluation of the potential in vivo relevance of in vitro data employing talinolol as model compound. Int J Clin Pharmacol Ther 36:16–24

    PubMed  CAS  Google Scholar 

  • Sperber I (1959) Secretion of organic anions in formation of urine and bile. Pharmacol Rev 11:109–134

    PubMed  CAS  Google Scholar 

  • Stein W (1967) (ed) The movement of molecules across membranes. Academic Press, New York, pp 367

    Google Scholar 

  • Sweet DH, Wolff NA, Pritchard JB (1997) Expression cloning and characterization of ROAT1 The basolateral organic anion transporter in rat kidney. J Biol Chem 272:30088–30095

    PubMed  CAS  Google Scholar 

  • Synold TW, Dussault I, Forman BM (2001) The orphan nuclear receptor SXR coordinately regulated drug metabolism and efflux. Nature Med 7:584–590

    PubMed  CAS  Google Scholar 

  • Tirona RG, Kim RB (2002) Pharmacogenomics of drug transporters. In: J Licinio, M-L Wing (eds) Pharmacogenomics: the search for individualized therapies. Wiley-VCH, pp 179–213

  • Tirona RG, Leake BF, Merino G, Kim RB (2001) Polymorphisms in OATP-C: Identification of multispecific allelic variants associated with altered transport activity among European- and African-Americans. J Biol Chem 276:35669–35675

    PubMed  CAS  Google Scholar 

  • Trauner M, Boyer JL (2003) Bile salt transporters: molecular characterization, function, and regulation. Physiol Rev 83:633–671

    PubMed  CAS  Google Scholar 

  • Trauner M, Meier PJ, Boyer JL (1998) Molecular pathogenesis of cholestasis. N Engl J Med 339:1217–1227

    PubMed  CAS  Google Scholar 

  • Trauner M, Wagner M, Fickert P, Zollner G (2005) Molecular regulation of hepatobiliary transport systems: clinical implications for understanding and treating cholestasis. J Clin Gastroenterol 39:S111–S124

    PubMed  Google Scholar 

  • Ullrich KJ (1997) Renal transporters for organic anions and organic cations. Structural requirements for substrates. J Membr Biol 158:95–107

    PubMed  CAS  Google Scholar 

  • Van Heeswijk RP, Veldkamp A, Mulder JW, Meenhorst PL, Lange JM, Beijnen JH, Hoetelmans RM (2001) Combination of protease inhibitors for the treatment of HIV-1-infected patients: a review of pharmacokinetics and clinical experience. J Antivir Ther 6:201–229

    Google Scholar 

  • Van Montfoort JE, Hagenbuch B, Groothuis GMM, Koepsell H, Meier PJ, Meijer DKF (2003) Drug uptake systems in liver and kidney. Curr Drug Metab 4:185–211

    PubMed  Google Scholar 

  • Wagner M, Trauner M (2005) Transcriptional regulation of hepatobiliary transport systems in health and disease: implications for a rationale approach to the treatment of intrahepatic cholestasis. Ann Hepatol 4:77–99

    PubMed  CAS  Google Scholar 

  • Wandel C, Kim RB, Kajiji S, Guengerich FP, Wilkinson GR, Wood AJJ (1999) P-glycoprotein and cytochrome P-450 3 A inhibition: dissociation of inhibitory potencies. Cancer Res 59:3944–3948

    PubMed  CAS  Google Scholar 

  • Ward WJ III (1970) Electrically induced carrier transport. Nature 227:162–163

    PubMed  CAS  Google Scholar 

  • Washington CB, Wiltshire HR, Man M, Moy T, Harris SR, Worth E, Weigl P, Liand Z, Hall D, Marriot L, Blaschke TF (2000) The disposition of saquinavir, in normal and P-glycoprotein deficient mice, rats, and cultured cells. Drug Metab Disp 28:1058–1062

    CAS  Google Scholar 

  • Watson P, Jones AT, Stephens DJ (2005) Intracellular trafficking pathways and drug delivery: fluorescence imaging of living and fixed cells. Adv Drug Deliv Rev 57:43–61

    PubMed  CAS  Google Scholar 

  • Weaver JL, Pine PS, Aszalos A, Schoenlein PV, Currier SJ, Padmanabhan R, Gottesman MM (1991) Laser scanning and confocal microscopy of daunorubicin, doxorubicin, and rhodamine 123 in multi-drug resistant cells. Exp Cell Res 196:323–329

    PubMed  CAS  Google Scholar 

  • Westphal K, Weinbrenner A, Zschiesche M, Franke G, Knoke M, Oertel R, Fritz P, von Richter O, Warzok R, Hachenberg T, Kaumann HM, Schrenk D, Terhaag B, Kroemer HK, Siegmund W (2000) Induction of P-glycoprotein by rifampin increases intestinal secretion of talinolol in human beings: a new type of drug/drug interaction. Clinical Pharmacol Ther 68:345–355

    CAS  Google Scholar 

  • Wilbrandt W (1975) Criteria in carrier transport. In: H Eisenberg, E Katchalski-Kazir, LA Manson (eds) Biomembranes vol 7. Plenum Press New York, London, pp 11–31

    Google Scholar 

  • Williams RT (1959) (ed) Detoxification mechanisms the metabolism and detoxification of drugs, toxic substances and other organic compounds. Chapman & Hall, London, pp 796

    Google Scholar 

  • Wright EM, Turk E (2004) The sodium/glucose cotransport family SLC5. Pflügers Arch-Eur J Physiol 447:510–518

    CAS  Google Scholar 

  • Yarim M, Moro S, Huber R, Meier PJ, Kaseda C, Kashima T, Hagenbuch B, Folkers G (2005) Application of QSAR analysis to organic anion polypeptide 1a5 (Oatp 1a5) substrates. Bioorg Med Chem 13:463–471

    PubMed  CAS  Google Scholar 

  • Zhang Y, Guo X, Tin ET, Benet LZ (1998) Overlapping substrate specificities of cytochrome P450 3A and P-glycoprotein for a novel cysteine protease inhibitor. Drug Metab Disp 26:360–366

    CAS  Google Scholar 

  • Ziegler K, Hummelsiep S (1993) Hepatoselective carrier-mediated sodium-independent uptake of pravastatin and pravastatin-lactone. Biochim Biophys Acta 1153:23–33

    PubMed  CAS  Google Scholar 

  • Ziegler K, Stünkel W (1992) Tissue-selective action of pravastatin due to hepatocellular uptake via a sodium-independent bile acid transporter. Biochim Biophys Acta 1139:203–209

    PubMed  CAS  Google Scholar 

  • What is the process of drug absorption?

    The most common mechanism of absorption for drugs is passive diffusion. This process can be explained through the Fick law of diffusion, in which the drug molecule moves according to the concentration gradient from a higher drug concentration to a lower concentration until equilibrium is reached.

    What is pharmacokinetics process?

    Pharmacokinetics (PK) is the study of how the body interacts with administered substances for the entire duration of exposure (medications for the sake of this article). This is closely related to but distinctly different from pharmacodynamics, which examines the drug's effect on the body more closely.

    How are drugs transported in the body?

    Drugs ingested into the body are transported through the plasma membrane several times. Although hydrophobic low molecules may penetrate the cell membrane according to simple diffusion, most drugs need carrier proteins named transporters for their trans-membrane transport.

    Is the movement of a drug into the bloodstream?

    Absorption refers to the movement of a drug from its site of administration to the bloodstream.