Targeting intestinal transporters for optimizing oral drug absorption

Current Drug Metabolism

Volumn 11, Issue 9, 2010, Pages 730-742

  Varma, Manthena V ^a   Ambler, Catherine M ^a   Ullah, Mohammad ^b   Rotter, Charles J ^a   Sun, Hao ^a   Litchfield, John ^a   Fenner, Katherine S ^b   El Kattan, Ayman F ^a  

^a PFIZER INC   (United States)

^b PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

Author keywords

Biopharmaceutics drug dispostion classificaiton system; Breast cancer resistance transporters; Monocarboxy late carrier transporter 1; Organic anion polypeptide transporters; P glycoprotein; Peptide transporter 1

Indexed keywords

ABACAVIR; ABC TRANSPORTER; AMINO ACID TRANSPORTER; AMPICILLIN; BREAST CANCER RESISTANCE PROTEIN; CARRIER PROTEIN; CERIVASTATIN; DACTINOMYCIN; DAUNORUBICIN; EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 1; EQUILIBRATIVE NUCLEOSIDE TRANSPORTER 2; FEXOFENADINE; GLYCOPROTEIN P; HYDROGEN; INDINAVIR; L TYPE AMINO ACID TRANSPORTER 1; L TYPE AMINO ACID TRANSPORTER 2; MONOCARBOXYLATE TRANSPORTER 1; MULTIDRUG RESISTANCE PROTEIN 1; MULTIDRUG RESISTANCE PROTEIN 2; MULTIDRUG RESISTANCE PROTEIN 3; MULTIDRUG RESISTANCE PROTEIN 4; ORGANIC ANION TRANSPORTER 1; PEPTIDE TRANSPORTER 1; SLC22A4 PROTEIN; SLC22A5 PROTEIN; SLC36A1 PROTEIN; SLC5A6 PROTEIN; SLCO2B1 PROTEIN; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ARTICLE; BINDING AFFINITY; BIOPHARMACEUTIC CLASSIFICATION SYSTEM; BIOPHARMACEUTIC DRUG DISPOSITION CLASSIFICATION SYSTEM; CELL POLARITY; CLASSIFICATION; CORRELATION ANALYSIS; CRYSTAL STRUCTURE; DRUG ABSORPTION; DRUG CLEARANCE; DRUG PENETRATION; DRUG SOLUBILITY; DRUG UPTAKE; HUMAN; HYDROGEN BOND; HYDROPHILICITY; IN VITRO STUDY; INTESTINE ABSORPTION; LIPOPHILICITY; PHARMACOPHORE; PHYSICOCHEMICAL MODEL; PROCESS OPTIMIZATION;

ADMINISTRATION, ORAL; ANIMALS; BIOLOGICAL AVAILABILITY; HUMANS; INTESTINAL ABSORPTION; INTESTINAL MUCOSA; INTESTINES; MEMBRANE TRANSPORT PROTEINS; MODELS, BIOLOGICAL; PHARMACEUTICAL PREPARATIONS; PHARMACOKINETICS; PRODRUGS;

EID: 79851494257     PISSN: 13892002     EISSN: None     Source Type: Journal    
DOI: 10.2174/138920010794328850     Document Type: Article

References (174)

1. Hughes, J. D.; Blagg, J.; Price, D. A.; Bailey, S.; Decrescenzo, G. A.; Devraj, R. V.; Ellsworth, E.; Fobian, Y. M.; Gibbs, M. E.; Gilles, R. W.; Greene, N.; Huang, E.; Krieger-Burke, T.; Loesel, J.; Wager, T.; Whiteley, L.; Zhang, Y. Physiochemical drug properties associated with in. vivo toxicological outcomes. Bioorg. Med. Chem. Lett., 2008, 18, 4872-4875.
2. Lipinski, C. A. Drug-like properties and the causes of poor solubility and poor permeability. J. Pharmacol. Tox. Methods., 2000, 44, 235-249. (Pubitemid 32239479)
3. Hurst, S.; Loi, C. M.; Brodfuehrer, J.; El-Kattan, A. Impact of physiological, physicochemical and biopharmaceutical factors in absorption and metabolism mechanisms on the drug oral bioavail-ability of rats and humans. Expert. Opin. Drug Metab. Toxicol., 2007, 3, 469-489. (Pubitemid 351324958)
4. Thomas, V. H.; Bhattachar, S.; Hitchingham, L.; Zocharski, P.; Naath, M.; Surendran, N.; Stoner, C. L.; El-Kattan, A. The road map to oral bioavailability: An industrial perspective. Expert. Opin. Drug Metab. Toxicol., 2006, 2, 591-608. (Pubitemid 46127071)
5. Varma, M. V.; Feng, B.; Obach, R. S.; Troutman, M. D.; Chupka, J.; Miller, H. R.; El-Kattan, A. Physicochemical determinants of human renal clearance. J. Med. Chem., 2009, 52, 4844-4852.
6. Varma, M. V.; Obach, R. S.; Rotter, C.; Miller, H. R.; Chang, G.; Steyn, S. J.; El-Kattan, A.; Troutman, M. D. Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination. J. Med. Chem., 2010, 53, 1098-1108.
7. Comess, K. M.; Schurdak, M. E. Affinity-based screening techniques for enhancing lead discovery. Curr. Opin. Drug Disc. Develop., 2004, 7, 411-416. (Pubitemid 44383547)
8. Kola, I.; Landis, J. Can the pharmaceutical industry reduce attrition rates? Nat. Rev. Drug Discov., 2004, 3, 711-715. (Pubitemid 39173511)
9. Stevens, J. L.; Baker, T. K. The future of drug safety testing: expanding the view and narrowing the focus. Drug Discov. Today., 2009, 14, 162-167.
10. Krejsa, C. M.; Horvath, D.; Rogalski, S. L.; Penzotti, J. E.; Mao, B.; Barbosa, F.; Migeon, J. C. Predicting ADME properties and side effects: the BioPrint approach. Curr. Opin. Drug Discov. Devel., 2003, 6, 470-480. (Pubitemid 36975350)
11. Kramer, J. A.; Sagartz, J. E.; Morris, D. L. The application of discovery toxicology and pathology towards the design of safer pharmaceutical lead candidates. Nat. Rev. Drug Discov., 2007, 6, 636-649. (Pubitemid 47207750)
12. Price, D. A.; Blagg, J.; Jones, L.; Greene, N.; Wager, T. Physico-chemical drug properties associated with in. vivo toxicological outcomes: a review. Expert. Opin. Drug Metab. Toxicol., 2009, 5, 921-931.
13. Jenkins, K. M.; Angeles, R.; Quintos, M. T.; Xu, R.; Kassel, D. B.; Rourick, R. A. Automated high throughput ADME assays for metabolic stability and cytochrome P450 inhibition profiling of combinatorial libraries. J. Pharm. Biomed. Anal., 2004, 34, 989-1004. (Pubitemid 38296402)
14. Kerns, E. H. High throughput physicochemical profiling for drug discovery. J. Pharm. Sci., 2001, 90, 1838-1858. (Pubitemid 33062605)
15. Masimirembwa, C. M.; Bredberg, U.; Andersson, T. B. Metabolic stability for drug discovery and development: pharmacokinetic and biochemical challenges. Clin. Pharmacokinet., 2003, 42, 515-528. (Pubitemid 36801870)
16. Amidon, G. L.; Lennernas, H.; Shah, V. P.; Crison, J. R. A theoretical basis for a biopharmaceutic drug classification: the correlation of in. vitro drug product dissolution and in. vivo bioavailability. Pharm. Res., 1995, 12, 413-420.
17. Benet, L. Z. The drug transporter-metabolism alliance: uncovering and defining the interplay. Mol. Pharm., 2009, 6, 1631-1643.
18. Custodio, J. M.; Wu, C. Y.; Benet, L. Z. Predicting drug disposition, absorption/elimination/transporter interplay and the role of food on drug absorption. Adv. Drug Deliv. Rev., 2008, 60, 717-733.
19. Wu, C. Y.; Benet, L. Z. Predicting drug disposition via application of BCS: transport/absorption/elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm. Res., 2005, 22, 11-23. (Pubitemid 40558141)
20. Fahr, A.; Liu, X. Drug delivery strategies for poorly water-soluble drugs. Expert. Opin. Drug Deliv., 2007, 4, 403-416. (Pubitemid 47249138)
21. Jain, D.; Pathak, D.; Pathak, K. Pharmaceutical product development technologies based on the biopharmaceutical classification system. Pharmazie., 2009, 64, 483-490.
22. Tsuji, A.; Tamai, I. Carrier-mediated intestinal transport of drugs. Pharm. Res., 1996, 13, 963-977. (Pubitemid 26258994)
23. Larsen, M.; Holm, R.; Jensen, K. G.; Brodin, B.; Nielsen, C. U. Intestinal gaboxadol absorption via PAT1 (SLC36A1): modified absorption in. vivo following co-administration of L-tryptophan. Br. J. Pharmacol., 2009, 157, 1380-1389.
24. Larsen, M.; Larsen, B. B.; Frolund, B.; Nielsen, C. U. Transport of amino acids and GABA analogues via the human proton-coupled amino acid transporter, hPAT1: characterization of conditions for affinity and transport experiments in Caco-2 cells. Eur. J. Pharm. Sci., 2008, 35, 86-95.
25. Yamamoto, A.; Akanuma, S.; Tachikawa, M.; Hosoya, K. Involvement of LAT1 and LAT2 in the high-and low-affinity transport of L-leucine in human retinal pigment epithelial cells (ARPE-19 cells). J. Pharm. Sci., 2010, 99, 2475-2482.
26. Cao, X.; Gibbs, S. T.; Fang, L.; Miller, H. A.; Landowski, C. P.; Shin, H. C.; Lennernas, H.; Zhong, Y.; Amidon, G. L.; Yu, L. X.; Sun, D. Why is it challenging to predict intestinal drug absorption and oral bioavailability in human using rat model. Pharm. Res., 2006, 23, 1675-1686. (Pubitemid 44200529)
27. Englund, G.; Rorsman, F.; Ronnblom, A.; Karlbom, U.; Lazorova, L.; Grasjo, J.; Kindmark, A.; Artursson, P. Regional levels of drug transporters along the human intestinal tract: co-expression of ABC and SLC transporters and comparison with Caco-2 cells. Eur. J. Pharm. Sci., 2006, 29, 269-277. (Pubitemid 44602404)
28. Sun, D.; Lennernas, H.; Welage, L. S.; Barnett, J. L.; Landowski, C. P.; Foster, D.; Fleisher, D.; Lee, K. D.; Amidon, G. L. Comparison of human duodenum and Caco-2 gene expression profiles for 12, 000 gene sequences tags and correlation with permeability of 26 drugs. Pharm. Res., 2002., 19, 1400-1416. (Pubitemid 35266543)
29. Giacomini, K. M.; Huang, S. M.; Tweedie, D. J.; Benet, L. Z.; Brou-wer, K. L.; Chu, X.; Dahlin, A.; Evers, R.; Fischer, V.; Hillgren, K. M.; Hoffmaster, K. A.; Ishikawa, T.; Keppler, D.; Kim, R. B.; Lee, C. A.; Niemi, M.; Polli, J. W.; Sugiyama, Y.; Swaan, P. W.; Ware, J. A.; Wright, S. H.; Yee, S. W.; Zamek-Gliszczynski, M. J.; Zhang, L. Membrane transporters in drug development. Nat. Rev. Drug Discov., 2010, 9, 215-236.
30. Benet, L. Z. Predicting drug disposition via application of a Biopharmaceutics Drug Disposition Classification System. Basic. Clin. Pharmacol. Toxicol., 2010, 106, 162-167.
31. Shugarts, S.; Benet, L. Z. The role of transporters in the pharma-cokinetics of orally administered drugs. Pharm. Res., 2009, 26., 2039-2054.
32. Juliano, R. L.; Ling, L. A surface glycoprotien on modulating drug permeability in chinease hamster overy cell mutants. Biochim. Bio-phys. Acta., 1976, 555, 152-162.
33. Ambudkar, S. V.; Dey, S.; Hrycyna, C. A.; Ramchandra, M.; Pastan, I.; Gottesman, M. M. Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu. Rev. Pharmacol. Toxi-col., 1999, 39, 361-398. (Pubitemid 29222564)
34. Schinkel, A. H.; Kemp, S.; Dolle, M.; Rudenco, G.; Wagenaar, E. N-glycosylation and deletion mutants of the human MDR1. P-glycoprotein. J. Biol. Chem., 1993, 268, 7474-7481. (Pubitemid 23105645)
35. Aller, S. G.; Yu, J.; Ward, A.; Weng, Y.; Chittaboina, S.; Zhuo, R.; Harrell, P. M.; Trinh, Y. T.; Zhang, Q.; Urbatsch, I. L.; Chang, G. Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science., 2009, 323, 1718-1722.
36. Shapiro, A. B.; Ling, V. Positively cooperative sites for drug transport by P-glycoprotein with distinct drug specificities. Eur. J. Biochem., 1997, 250, 130-137. (Pubitemid 27504592)
37. Shapiro, A. B.; Fox, K.; Lam, P.; Ling, V. Stimulation of P-glycoprotein-mediated drug transport by prazosin and progesterone. Evidence for a third drug-binding site. Eur. J. Biochem., 1999, 259, 841-850. (Pubitemid 29075514)
38. Acharya, P.; Tran, T. T.; Polli, J. W.; Ayrton, A.; Ellens, H.; Bentz, J. P-Glycoprotein (P-gp) expressed in a confluent monolayer of hMDR1-MDCKII cells has more than one efflux pathway with cooperative binding sites. Biochemistry., 2006, 45, 15505-15519. (Pubitemid 46032474)
39. Thiebut, F.; Tsuruo, T.; Hamada, H.; Gottesman, M. M.; Pastan, I. Celluar localisation of the multidrug resistance gene product P-glycoprotien in normal human tissues. Proc. Natl. Acad. Sci. USA, 1987, 84, 7735-7738.
40. Mahar Doan, K. M.; Humphreys, J. E.; Webster, L. O.; Wring, S. A.; Shampine, L. J.; Serabjit-Singh, C. J.; Adkison, K. K.; Polli, J. W. Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J. Pharmacol. Exp. Ther., 2002, 303, 1029-1037. (Pubitemid 35424386)
41. Polli, J. W.; Wring, S. A.; Humphreys, J. E.; Huang, L.; Morgan, J. B.; Webster, L. O.; Serabjit-Singh, C. S. Rational use of in. vitro P-glycoprotein assays in drug discovery. J. Pharmacol. Exp. Ther., 2001, 299, 620-628. (Pubitemid 32979675)
42. Takano, M.; Yumoto, R.; Murakami, T. Expression and function of efflux drug transporters in the intestine. Pharmacol. Ther., 2006, 109, 137-161. (Pubitemid 41740818)
43. Varma, M. V. S.; Ashokraj, Y.; Dey, C. S.; Panchagnula, R. P-glycoprotein inhibitors and their screening: a perspective from bioavailability enhancement. Pharmacol. Res., 2003, 48, 347-359. (Pubitemid 36945333)
44. Fenner, K. S.; Troutman, M. D.; Kempshall, S.; Cook, J. A.; Ware, J. A.; Smith, D. A.; Lee, C. A. Drug-drug interactions mediated through P-glycoprotein: clinical relevance and in. vitro-in. vivo correlation using digoxin as a probe Drug Clin. Pharmacol. Ther., 2009, 85, 173-181.
45. Gramatte, T.; Oertel, R.; Terhaag, B.; Kirch, W. Direct demonstration of small intestinal secretion and site-dependent absorption of the beta-blocker talinolol in humans. Clin. Pharmacol. Ther., 1996, 59, 541-549. (Pubitemid 26191376)
46. Greiner, B.; Eichelbaum, M.; Fritz, P.; Kreichgauer, H. P.; von Richter, O.; Zundler, J.; Kroemer, H. K. The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. J. Clin. Invest., 1999, 104, 147-153.
47. Westphal, K.; Weinbrenner, A.; Zschiesche, M.; Franke, G.; Knoke, M.; Oertel, R.; Fritz, P.; von Richter, O.; Warzok, R.; Hachenberg, T.; Kauffmann, H. M.; Schrenk, D.; Terhaag, B.; Kro-emer, H. K.; Siegmund, W. Induction of P-glycoprotein by rifampin increases intestinal secretion of talinolol in human beings: a new type of drug/drug interaction. Clin. Pharmacol. Ther., 2000, 68, 345-355.
48. Cascorbi, I.; Gerloff, T.; Johne, A.; Meisel, C.; Hoffmeyer, S.; Schwab, M.; Schaeffeler, E.; Eichelbaum, M.; Brinkmann, U.; Roots, I. Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects. Clin. Pharmacol. Ther., 2001, 69, 169-174. (Pubitemid 32225417)
49. Hoffmeyer, S.; Burk, O.; von Richter, O.; Arnold, H. P.; Brock-moller, J.; Johne, A.; Cascorbi, I.; Gerloff, T.; Roots, I.; Eichel-baum, M.; Brinkmann, U. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in. vivo. Proc. Natl. Acad. Sci. USA, 2000, 97, 3473-3478. (Pubitemid 30183327)
50. Marzolini, C.; Paus, E.; Buclin, T.; Kim, R. B. Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin. Pharmacol. Ther., 2004, 75, 13-33. (Pubitemid 38130115)
51. Cho, H. Y.; Yoo, H. D.; Lee, Y. B. Influence of ABCB1 genetic polymorphisms on the pharmacokinetics of levosulpiride in healthy subjects. Neuroscience., 2010, 169, 378-387.
52. Varma, M. V. S.; Khandavilli, S.; Ashokraj, Y.; Jain, A.; Dhanikula, A.; Sood, A.; Thomas, N. S.; Pillai, O. P.; Sharma, P.; Gandhi, R.; Agrawal, S.; Nair, V.; Panchagnula, R. Biopharmaceutic classification system:A scientific framework for pharmacokinetic optimization in drug research. Curr. Drug Metab., 2004, 5, 375-388. (Pubitemid 39276602)
53. Smith, B. J.; Doran, A. C.; McLean, S.; Tingley, F. D., 3rd; O'Neill, B. T.; Kajiji, S. M. P-glycoprotein efflux at the blood-brain barrier mediates differences in brain disposition and pharmacodynamics between two structurally related neurokinin-1 receptor antagonists. J. Pharmacol. Exp. Ther., 2001, 298, 1252-1259. (Pubitemid 32761947)
54. Whitlock, G. A.; Brennan, P. E.; Roberts, L. R.; Stobie, A. Potent and selective alpha1A adrenoceptor partial agonists-novel imida-zole frameworks. Bioorg. Med. Chem. Lett., 2009., 19, 3118-3121.
55. Sugano, K.; Kansy, M.; Artursson, P.; Avdeef, A.; Bendels, S.; Di, L.; Ecker, G. F.; Faller, B.; Fischer, H.; Gerebtzoff, G.; Lennernaes, H.; Senner, F. Coexistence of passive and carrier-mediated processes in drug transport. Nat. Rev. Drug Discov., 2010, 9, 597-614.
56. Varma, M. V.; Panchagnula, R. pH-dependent functional activity of P-glycoprotein in limiting intestinal absorption of protic drugs: kinetic analysis of quinidine efflux in situ. J. Pharm. Sci., 2005, 94, 2632-2643. (Pubitemid 43265387)
57. Varma, M. V.; Sateesh, K.; Panchagnula, R. Functional role of P-glycoprotein in limiting intestinal absorption of drugs: contribution of passive permeability to P-glycoprotein mediated efflux transport. Mol. Pharm., 2005, 2, 12-21. (Pubitemid 40314725)
58. Prueksaritanont, T.; DeLuna, P.; Gorham, L. M.; Ma, B.; Cohn, D.; Pang, J.; Xu, X.; Leung, K.; Lin, J. H. In. vitro and in. vivo evaluations of intestinal barriers for the zwitterion L-767, 679 and its car-boxyl ester prodrug L-775, 318. Roles of efflux and metabolism. Drug Metab. Dispos., 1998, 26, 520-527. (Pubitemid 28498356)
59. Ouyang, H.; Tang, F.; Siahaan, T. J.; Borchardt, R. T. A modified coumarinic acid-based cyclic prodrug of an opioid peptide: its enzymatic and chemical stability and cell permeation characteristics. Pharm. Res., 2002., 19, 794-801. (Pubitemid 34686738)
60. Tang, F.; Borchardt, R. T. Characterization of the efflux trans-porter (s) responsible for restricting intestinal mucosa permeation of an acyloxyalkoxy-based cyclic prodrug of the opioid peptide DADLE. Pharm. Res., 2002., 19, 780-786. (Pubitemid 34686736)
61. Seelig, A.; Landwojtowicz, E. Structure-activity relationship of P-glycoprotein substrates and modifiers. Eur. J. Pharm. Sci., 2000, 12, 31-40.
62. Seelig, A. A general pattern for substrate recognition by P-glycoprotein. Eur. J. Biochem., 1998, 251, 252-261. (Pubitemid 28081437)
63. Seelig, A. How does P-glycoprotein recognize its substrates? Int. J. Clin. Pharmacol. Ther., 1998, 36, 50-54. (Pubitemid 28031809)
64. Didziapetris, R.; Japertas, P.; Avdeef, A.; Petrauskas, A. Classification analysis of P-glycoprotein substrate specificity. J. Drug Target., 2003, 11, 391-406. (Pubitemid 38455825)
65. Cabrera, M. A.; Gonzalez, I.; Fernandez, C.; Navarro, C.; Bermejo, M. A topological substructural approach for the prediction of P-glycoprotein substrates. J. Pharm. Sci., 2006, 95, 589-606.
66. Huang, J.; Ma, G.; Muhammad, I.; Cheng, Y. Identifying P-glycoprotein substrates using a support vector machine optimized by a particle swarm. J. Chem. Inf. Model., 2007, 47, 1638-1647. (Pubitemid 47210067)
67. Stouch, T. R.; Gudmundsson, O. Progress in understanding the structure-activity relationships of P-glycoprotein. Adv. Drug Deliv. Rev., 2002, 54, 315-328. (Pubitemid 34260956)
68. Staud, F.; Pavek, P. Breast cancer resistance protein (BCRP/ABCG2). Int. J. Biochem. Cell Biol., 2005, 37, 720-725. (Pubitemid 40202994)
69. Graf, G. A.; Yu, L.; Li, W. P.; Gerard, R.; Tuma, P. L.; Cohen, J. C.; Hobbs, H. H. ABCG5 and ABCG8 are obligate heterodimers for protein trafficking and biliary cholesterol excretion. J. Biol. Chem., 2003, 278, 48275-48282. (Pubitemid 37523283)
70. Hazai, E.; Bikadi, Z. Homology modeling of breast cancer resistance protein (ABCG2). J. Struct. Biol., 2008, 162, 63-74.
71. Muenster, U.; Grieshop, B.; Ickenroth, K.; Gnoth, M. J. Characterization of substrates and inhibitors for the in. vitro assessment of Bcrp mediated drug-drug interactions. Pharm. Res., 2008, 25, 2320-2326.
72. Rosenberg, M. F.; Bikadi, Z.; Chan, J.; Liu, X.; Ni, Z.; Cai, X.; Ford, R. C.; Mao, Q. The human breast cancer resistance protein (BCRP/ABCG2) shows conformational changes with mitoxan-trone. Structure., 2010, 18, 482-493.
73. Cai, X.; Bikadi, Z.; Ni, Z.; Lee, E. W.; Wang, H.; Rosenberg, M. F.; Mao, Q. Role of basic residues within or near the predicted trans-membrane helix 2 of the human breast cancer resistance protein in drug transport. J. Pharmacol. Exp. Ther., 2010, 333, 670-681.
74. Doyle, L. A.; Ross, D. D. Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2). Oncogene, 2003, 22, 7340-7358. (Pubitemid 37487163)
75. Bruyere, A.; Decleves, X.; Bouzom, F.; Ball, K.; Marques, C.; Treton, X.; Pocard, M.; Valleur, P.; Bouhnik, Y.; Panis, Y.; Scherrmann, J. M.; Mouly, S. Effect of Variations in the Amounts of P-Glycoprotein (ABCB1), BCRP (ABCG2) and CYP3A4 along the Human Small Intestine on PBPK Models for Predicting Intestinal First Pass. Mol. Pharm., 2010, 7,. 1596-1607.
76. Taipalensuu, J.; Tornblom, H.; Lindberg, G.; Einarsson, C.; Sjo-qvist, F.; Melhus, H.; Garberg, P.; Sjostrom, B.; Lundgren, B.; Ar-tursson, P. Correlation of gene expression of ten drug efflux proteins of the ATP-binding cassette transporter family in normal human jejunum and in human intestinal epithelial Caco-2 cell mono-layers. J. Pharmacol. Exp. Ther., 2001, 299, 164-170. (Pubitemid 32905131)
77. Zaher, H.; Khan, A. A.; Palandra, J.; Brayman, T. G.; Yu, L.; Ware, J. A. Breast cancer resistance protein (Bcrp/abcg2) is a major determinant of sulfasalazine absorption and elimination in the mouse. Mol. Pharm., 2006, 3, 55-61. (Pubitemid 43331751)
78. Bailey, K. M.; Romaine, S. P.; Jackson, B. M.; Farrin, A. J.; Efthymiou, M.; Barth, J. H.; Copeland, J.; McCormack, T.; White-head, A.; Flather, M. D.; Samani, N. J.; Nixon, J.; Hall, A. S.; Balm-forth, A. J. Hepatic metabolism and transporter gene variants enhance response to rosuvastatin in patients with acute myocardial infarction: the GEOSTAT-1 Study. Circ. Cardiovasc. Genet., 3, 276-285.
79. Huang, L.; Wang, Y.; Grimm, S. ATP-dependent transport of rosu-vastatin in membrane vesicles expressing breast cancer resistance protein. Drug Metab. Dispos., 2006, 34, 738-742.
80. Ieiri, I.; Higuchi, S.; Sugiyama, Y. Genetic polymorphisms of uptake (OATP1B1, 1B3) and efflux (MRP2, BCRP) transporters: implications for inter-individual differences in the pharmacokinet-ics and pharmacodynamics of statins and other clinically relevant drugs. Expert Opin. Drug Metab. Toxicol., 2009, 5, 703-729.
81. Merino, G.; Jonker, J. W.; Wagenaar, E.; Pulido, M. M.; Molina, A. J.; Alvarez, A. I.; Schinkel, A. H. Transport of anthelmintic ben-zimidazole drugs by breast cancer resistance protein (BCRP/ABCG2). Drug Metab. Dispos., 2005, 33, 614-618. (Pubitemid 40593873)
82. Ando, T.; Kusuhara, H.; Merino, G.; Alvarez, A. I.; Schinkel, A. H.; Sugiyama, Y. Involvement of breast cancer resistance protein (ABCG2) in the biliary excretion mechanism of fluoroquinolones. Drug Metab. Dispos., 2007, 35, 1873-1879. (Pubitemid 47481581)
83. Dauchy, S.; Miller, F.; Couraud, P. O.; Weaver, R. J.; Weksler, B.; Romero, I. A.; Scherrmann, J. M.; De Waziers, I.; Decleves, X. Expression and transcriptional regulation of ABC transporters and cy-tochromes P450 in hCMEC/D3 human cerebral microvascular en-dothelial cells. Biochem. Pharmacol., 2009, 77, 897-909.
84. Kruijtzer, C. M.; Beijnen, J. H.; Rosing, H.; ten Bokkel Huinink, W. W.; Schot, M.; Jewell, R. C.; Paul, E. M.; Schellens, J. H. Increased oral bioavailability of topotecan in combination with the breast cancer resistance protein and P-glycoprotein inhibitor GF120918. J. Clin. Oncol., 2002., 20, 2943-2950. (Pubitemid 34728888)
85. Yamasaki, Y.; Ieiri, I.; Kusuhara, H.; Sasaki, T.; Kimura, M.; Tabuchi, H.; Ando, Y.; Irie, S.; Ware, J.; Nakai, Y.; Higuchi, S.; Sugiyama, Y. Pharmacogenetic characterization of sulfasalazine disposition based on NAT2 and ABCG2 (BCRP) gene polymorphisms in humans. Clin. Pharmacol. Ther., 2008, 84, 95-103. (Pubitemid 351861490)
86. Keskitalo, J. E.; Pasanen, M. K.; Neuvonen, P. J.; Niemi, M. Different effects of the ABCG2 c.421C>A SNP on the pharmacokinetics of fluvastatin, pravastatin and simvastatin. Pharmacogenomics, 2009, 10, 1617-1624.
87. Keskitalo, J. E.; Zolk, O.; Fromm, M. F.; Kurkinen, K. J.; Neuvonen, P. J.; Niemi, M. ABCG2 polymorphism markedly affects the phar-macokinetics of atorvastatin and rosuvastatin. Clin. Pharmacol. Ther., 2009, 86., 197-203.
88. Merino, G.; Alvarez, A. I.; Pulido, M. M.; Molina, A. J.; Schinkel, A. H.; Prieto, J. G. Breast cancer resistance protein (BCRP/ABCG2) transports fluoroquinolone antibiotics and affects their oral availability, pharmacokinetics, and milk secretion. Drug Metab. Dis-pos., 2006, 34, 690-695.
89. Seamon, J. A.; Rugg, C. A.; Emanuel, S.; Calcagno, A. M.; Ambud-kar, S. V.; Middleton, S. A.; Butler, J.; Borowski, V.; Greenberger, L. M. Role of the ABCG2 drug transporter in the resistance and oral bioavailability of a potent cyclin-dependent kinase/Aurora kinase inhibitor. Mol. Cancer. Ther., 2006, 5, 2459-2467. (Pubitemid 44650909)
90. Yamagata, T.; Kusuhara, H.; Morishita, M.; Takayama, K.; Benameur, H.; Sugiyama, Y. Improvement of the oral drug absorption of topotecan through the inhibition of intestinal xenobiotic efflux transporter, breast cancer resistance protein, by excipients. Drug Metab. Dispos., 2007, 35, 1142-1148. (Pubitemid 46956435)
91. Zaher, H.; Khan, A. A.; Palandra, J.; Brayman, T. G.; Yu, L.; Ware, J. A. Breast cancer resistance protein (Bcrp/abcg2) is a major determinant of sulfasalazine absorption and elimination in the mouse. Mol. Pharm., 2006, 3, 55-61. (Pubitemid 43331751)
92. Matsson, P.; Englund, G.; Ahlin, G.; Bergstrom, C. A.; Norinder, U.; Artursson, P. A global drug inhibition pattern for the human ATP-binding cassette transporter breast cancer resistance protein (ABCG2). J. Pharmacol. Exp. Ther., 2007, 323., 19-30. (Pubitemid 47443263)
93. Matsson, P.; Pedersen, J. M.; Norinder, U.; Bergstrom, C. A.; Ar-tursson, P. Identification of novel specific and general inhibitors of the three major human ATP-binding cassette transporters P-gp, BCRP and MRP2 among registered drugs. Pharm. Res., 2009, 26, 1816-1831.
94. Nicolle, E.; Boumendjel, A.; Macalou, S.; Genoux, E.; Ahmed-Belkacem, A.; Carrupt, P. A.; Di Pietro, A. QSAR analysis and molecular modeling of ABCG2-specific inhibitors. Adv. Drug Deliv. Rev., 2009, 61, 34-46.
95. Saito, H.; Hirano, H.; Nakagawa, H.; Fukami, T.; Oosumi, K.; Murakami, K.; Kimura, H.; Kouchi, T.; Konomi, M.; Tao, E.; Tsu-jikawa, N.; Tarui, S.; Nagakura, M.; Osumi, M.; Ishikawa, T. A new strategy of high-speed screening and quantitative structure-activity relationship analysis to evaluate human ATP-binding cassette transporter ABCG2-drug interactions. J. Pharmacol. Exp. Ther., 2006, 317, 1114-1124. (Pubitemid 43764115)
96. Yoshikawa, M.; Ikegami, Y.; Hayasaka, S.; Ishii, K.; Ito, A.; Sano, K.; Suzuki, T.; Togawa, T.; Yoshida, H.; Soda, H.; Oka, M.; Kohno, S.; Sawada, S.; Ishikawa, T.; Tanabe, S. Novel camptothe-cin analogues that circumvent ABCG2-associated drug resistance in human tumor cells. Int. J. Cancer, 2004, 110, 921-927. (Pubitemid 38758521)
97. Nakagawa, H.; Saito, H.; Ikegami, Y.; Aida-Hyugaji, S.; Sawada, S.; Ishikawa, T. Molecular modeling of new camptothecin analogues to circumvent ABCG2-mediated drug resistance in cancer. Cancer. Lett., 2006, 234, 81-89. (Pubitemid 43343942)
98. Kaliszczak, M.; Antonow, D.; Patel, K. I.; Howard, P.; Jodrell, D. I.; Thurston, D. E.; Guichard, S. M. Optimization of the antitumor activity of sequence-specific pyrrolobenzodiazepine derivatives based on their affinity for ABC transporters. AAPS J., 2010, 12,. 617-627.
99. Begley, D. J. ABC transporters and the blood-brain barrier. Curr. Pharm. Des., 2004, 10, 1295-1312. (Pubitemid 38559749)
100. Kunta, J. R.; Sinko, P. J. Intestinal drug transporters: in. vivo function and clinical importance. Curr. Drug Metab., 2004, 5, 109-124. (Pubitemid 38292004)
101. Fei, Y. J.; Kanai, Y.; Nussberger, S.; Ganapathy, V.; Leibach, F. H.; Romero, M. F.; Singh, S. K.; Boron, W. F.; Hediger, M. A. Expression cloning of a mammalian proton-coupled oligopeptide transporter. Nature, 1994, 368, 563-566. (Pubitemid 24118776)
102. Liang, R.; Fei, Y. J.; Prasad, P. D.; Ramamoorthy, S.; Han, H.; Yang-Feng, T. L.; Hediger, M. A.; Ganapathy, V.; Leibach, F. H. Human intestinal H+/peptide cotransporter. Cloning, functional expression, and chromosomal localization. J. Biol. Chem., 1995, 270, 6456-6463.
103. Rubio-Aliaga, I.; Daniel, H. Peptide transporters and their roles in physiological processes and drug disposition. Xenobiotica, 2008, 38, 1022-1042.
104. Herrera-Ruiz, D.; Wang, Q.; Gudmundsson, O. S.; Cook, T. J.; Smith, R. L.; Faria, T. N.; Knipp, G. T. Spatial expression patterns of peptide transporters in the human and rat gastrointestinal tracts, Caco-2 in vitro cell culture model, and multiple human tissues. AAPS PharmSci., 2001, 3, E9.
105. Adibi, S. A. The oligopeptide transporter (Pept-1) in human intestine: biology and function. Gastroenterology, 1997, 113, 332-340. (Pubitemid 27281791)
106. Irie, M.; Terada, T.; Katsura, T.; Matsuoka, S.; Inui, K. Computational modelling of H+-coupled peptide transport via human PEPT1. J. Physiol., 2005, 565, 429-439. (Pubitemid 40872473)
107. Foley, D. W.; Rajamanickam, J.; Bailey, P. D.; Meredith, D. Bioavailability through PepT1: the role of computer modelling in intelligent drug design. Curr. Comput. Aided. Drug Des, 6, 68-78.
108. Meredith, D.; Price, R. A. Molecular modeling of PepT1-towards a structure. J. Membr. Biol., 2006, 213, 79-88.
109. Brandsch, M.; Knutter, I.; Leibach, F. H. The intestinal H+/peptide symporter PEPT1: structure-affinity relationships. Eur. J. Pharm. Sci., 2004, 21, 53-60. (Pubitemid 38050203)
110. Doring, F.; Walter, J.; Will, J.; Focking, M.; Boll, M.; Amasheh, S.; Clauss, W.; Daniel, H. Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications. J. Clin. Invest., 1998, 101, 2761-2767. (Pubitemid 28294585)
111. Vig, B. S.; Stouch, T. R.; Timoszyk, J. K.; Quan, Y.; Wall, D. A.; Smith, R. L.; Faria, T. N. Human PEPT1 pharmacophore distinguishes between dipeptide transport and binding. J. Med. Chem., 2006, 49, 3636-3644. (Pubitemid 43902468)
112. Omkvist, D. H.; Larsen, S. B.; Nielsen, C. U.; Steffansen, B.; Olsen, L.; Jorgensen, F. S.; Brodin, B. A quantitative structure-activity relationship for translocation of tripeptides via the human proton-coupled peptide transporter, hPEPT1 (SLC15A1). AAPS J., 2010, 12, 385-396.
113. Brandsch, M.; Knutter, I.; Thunecke, F.; Hartrodt, B.; Born, I.; Borner, V.; Hirche, F.; Fischer, G.; Neubert, K. Decisive structural determinants for the interaction of proline derivatives with the intestinal H+/peptide symporter. Eur. J. Biochem., 1999, 266, 502-508.
114. Knutter, I.; Wollesky, C.; Kottra, G.; Hahn, M. G.; Fischer, W.; Zebisch, K.; Neubert, R. H.; Daniel, H.; Brandsch, M. Transport of angiotensin- converting enzyme inhibitors by H+/peptide transporters revisited. J. Pharmacol. Exp. Ther., 2008, 327, 432-441.
115. Terada, T.; Saito, H.; Mukai, M.; Inui, K. Characterization of stably transfected kidney epithelial cell line expressing rat H+/peptide co-transporter PEPT1: localization of PEPT1 and transport of beta-lactam antibiotics. J. Pharmacol. Exp. Ther., 1997, 281, 1415-1421. (Pubitemid 27258402)
116. Watanabe, K.; Sawano, T.; Endo, T.; Sakata, M.; Sato, J. Studies on intestinal absorption of sulpiride (2): transepithelial transport of sulpiride across the human intestinal cell line Caco-2. Biol. Pharm. Bull., 2002, 25, 1345-1350. (Pubitemid 39663199)
117. Watanabe, K.; Sawano, T.; Jinriki, T.; Sato, J. Studies on intestinal absorption of sulpiride (3): intestinal absorption of sulpiride in rats. Biol. Pharm. Bull., 2004, 27, 77-81. (Pubitemid 41656677)
118. Watanabe, K.; Sawano, T.; Terada, K.; Endo, T.; Sakata, M.; Sato, J. Studies on intestinal absorption of sulpiride (1): carrier-mediated uptake of sulpiride in the human intestinal cell line Caco-2. Biol. Pharm. Bull., 2002, 25, 885-890. (Pubitemid 40022118)
119. Bretschneider, B.; Brandsch, M.; Neubert, R. Intestinal transport of beta-lactam antibiotics: analysis of the affinity at the H+/peptide symporter (PEPT1), the uptake into Caco-2 cell monolayers and the transepithelial flux. Pharm. Res., 1999, 16, 55-61. (Pubitemid 29047457)
120. Kikuchi, A.; Tomoyasu, T.; Tanaka, M.; Kanamitsu, K.; Sasabe, H.; Maeda, T.; Odomi, M.; Tamai, I. Peptide derivation of poorly absorbable drug allows intestinal absorption via peptide transporter. J. Pharm. Sci., 2009, 98, 1775-1787.
121. de Miranda, P.; Blum, M. R. Pharmacokinetics of acyclovir after intravenous and oral administration. J. Antimicrob. Chemother., 1983, 12 (Suppl. B), 29-37. (Pubitemid 14238677)
122. Soul-Lawton, J.; Seaber, E.; On, N.; Wootton, R.; Rolan, P.; Pos-ner, J. Absolute bioavailability and metabolic disposition of valaci-clovir, the L-valyl ester of acyclovir, following oral administration to humans. Antimicrob. Agents. Chemother., 1995, 39, 2759-2764.
123. Bueno, A. B.; Collado, I.; de Dios, A.; Dominguez, C.; Martin, J. A.; Martin, L. M.; Martinez-Grau, M. A.; Montero, C.; Pedregal, C.; Catlow, J.; Coffey, D. S.; Clay, M. P.; Dantzig, A. H.; Lindstrom, T.; Monn, J. A.; Jiang, H.; Schoepp, D. D.; Stratford, R. E.; Tabas, L. B.; Tizzano, J. P.; Wright, R. A.; Herin, M. F. Dipeptides as effective prodrugs of the unnatural amino acid (+)-2-aminobicyclo[3.1.0]hexane-2, 6-dicarboxylic acid (LY354740), a selective group II metabotropic glutamate receptor agonist. J. Med. Chem., 2005, 48, 5305-5320. (Pubitemid 41113916)
124. Varma, M. V.; Eriksson, A. H.; Sawada, G.; Pak, Y. A.; Perkins, E. J.; Zimmerman, C. L. Transepithelial transport of the group II me-tabotropic glutamate 2/3 receptor agonist (1S, 2S, 5R, 6S)-2-aminobicyclo[3.1.0]hexane-2, 6-dicarboxylate (LY354740) and its prodrug (1S, 2S, 5R, 6S)-2-[(2'S) - (2'-amino) propionyl]aminobicyclo [3.1.0]hexane-2, 6-d icarboxylate (LY544344). Drug Metab. Dispos., 2009, 37, 211-220.
125. Rubio-Aliaga, I.; Daniel, H. Mammalian peptide transporters as targets for drug delivery. Trends Pharmacol. Sci., 2002, 23, 434-440. (Pubitemid 35247773)
126. Hagenbuch, B.; Meier, P. J. Organic anion transporting polypep-tides of the OATP/SLC21 family: phylogenetic classification as OATP/SLCO superfamily, new nomenclature and molecular/functional properties. Pflugers Arch., 2004, 447, 653-665. (Pubitemid 38241451)
127. Kullak-Ublick, G. A.; Ismair, M. G.; Stieger, B.; Landmann, L.; Huber,
128. Tamai, I.; Nezu, J.; Uchino, H.; Sai, Y.; Oku, A.; Shimane, M.; Tsuji, A. Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem. Biophys. Res. Commun., 2000, 273, 251-260. (Pubitemid 30426895)
129. Hagenbuch, B.; Meier, P. J. The superfamily of organic anion transporting polypeptides. Biochim. Biophys. Acta., 2003, 1609, 1-18. (Pubitemid 36044060)
130. Sai, Y.; Kaneko, Y.; Ito, S.; Mitsuoka, K.; Kato, Y.; Tamai, I.; Artursson, P.; Tsuji, A. Predominant contribution of organic anion transporting polypeptide OATP-B (OATP2B1) to apical uptake of estrone-3-sulfate by human intestinal Caco-2 cells. Drug Metab. Dispos., 2006, 34, 1423-1431. (Pubitemid 44079886)
131. Kobayashi, D.; Nozawa, T.; Imai, K.; Nezu, J.; Tsuji, A.; Tamai, I. Involvement of human organic anion transporting polypeptide OATP-B (SLC21A9) in pH-dependent transport across intestinal apical membrane. J. Pharmacol. Exp. Ther., 2003, 306, 703-708. (Pubitemid 36886171)
132. Nozawa, T.; Imai, K.; Nezu, J.; Tsuji, A.; Tamai, I. Functional characterization of pH-sensitive organic anion transporting poly-peptide OATP-B in human. J. Pharmacol. Exp. Ther., 2004, 308, 438-445. (Pubitemid 38134202)
133. Meier-Abt, F.; Mokrab, Y.; Mizuguchi, K. Organic anion transporting polypeptides of the OATP/SLCO superfamily: identification of new members in nonmammalian species, comparative modeling and a potential transport mode. J. Membr. Biol., 2005., 208, 213-227.
134. Grube, M.; Kock, K.; Karner, S.; Reuther, S.; Ritter, C. A.; Jed-litschky, G.; Kroemer, H. K. Modification of OATP2B1-mediated transport by steroid hormones. Mol. Pharmacol., 2006, 70, 1735-1741.
135. Grube, M.; Kock, K.; Oswald, S.; Draber, K.; Meissner, K.; Eckel, L.; Bohm, M.; Felix, S. B.; Vogelgesang, S.; Jedlitschky, G.; Sieg-mund, W.; Warzok, R.; Kroemer, H. K. Organic anion transporting polypeptide 2B1 is a high-affinity transporter for atorvastatin and is expressed in the human heart. Clin. Pharmacol. Ther., 2006, 80, 607-620. (Pubitemid 44920223)
136. Satoh, H.; Yamashita, F.; Tsujimoto, M.; Murakami, H.; Koyabu, N.; Ohtani, H.; Sawada, Y. Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B. Drug Metab. Dispos., 2005, 33, 518-523. (Pubitemid 40393194)
137. Nozawa, T.; Nakajima, M.; Tamai, I.; Noda, K.; Nezu, J.; Sai, Y.; Tsuji, A.; Yokoi, T. Genetic polymorphisms of human organic an-ion transporters OATP-C (SLC21A6) and OATP-B (SLC21A9): allele frequencies in the Japanese population and functional analysis. J. Pharmacol. Exp. Ther., 2002, 302, 804-813. (Pubitemid 34787251)
138. Hanggi, E.; Grundschober, A. F.; Leuthold, S.; Meier, P. J.; St-Pierre, M. V. Functional analysis of the extracellular cysteine residues in the human organic anion transporting polypeptide, OATP2B1. Mol. Pharmacol., 2006, 70, 806-817. (Pubitemid 44268438)
139. Kullak-Ublick, G. A.; Hagenbuch, B.; Stieger, B.; Schteingart, C. D.; Hofmann, A. F.; Wolkoff, A. W.; Meier, P. J. Molecular and functional characterization of an organic anion transporting poly-peptide cloned from human liver. Gastroenterology, 1995, 109, 1274-1282.
140. Shimizu, M.; Fuse, K.; Okudaira, K.; Nishigaki, R.; Maeda, K.; Kusuhara, H.; Sugiyama, Y. Contribution of OATP (organic anion-transporting polypeptide) family transporters to the hepatic uptake of fexofenadine in humans. Drug Metab. Dispos., 2005, 33, 1477-1481. (Pubitemid 41323995)
141. Ianculescu, A. G.; Friesema, E. C.; Visser, T. J.; Giacomini, K. M.; Scanlan, T. S. Transport of thyroid hormones is selectively inhibited by 3-iodothyronamine. Mol. Biosyst., 2010, 6, 1403-1410.
142. Loubiere, L. S.; Vasilopoulou, E.; Bulmer, J. N.; Taylor, P. M.; Stieger, B.; Verrey, F.; McCabe, C. J.; Franklyn, J. A.; Kilby, M. D.; Chan, S. Y. Expression of thyroid hormone transporters in the human placenta and changes associated with intrauterine growth restriction. Placenta, 2010, 31, 295-304.
143. Geyer, J.; Doring, B.; Failing, K.; Petzinger, E. Molecular cloning and functional characterization of the bovine (Bos taurus) organic anion transporting polypeptide Oatp1a2 (Slco1a2). Comp. Biochem. Physiol. B. Biochem. Mol. Biol., 2004, 137, 317-329. (Pubitemid 38429744)
144. Kalliokoski, A.; Niemi, M. Impact of OATP transporters on phar-macokinetics. Br. J. Pharmacol., 2009, 158, 693-705.
145. Gao, B.; Hagenbuch, B.; Kullak-Ublick, G. A.; Benke, D.; Aguzzi, A.; Meier, P. J. Organic anion-transporting polypeptides mediate transport of opioid peptides across blood-brain barrier. J. Pharmacol. Exp. Ther., 2000, 294, 73-79. (Pubitemid 30434672)
146. Hsiang, B.; Zhu, Y.; Wang, Z.; Wu, Y.; Sasseville, V.; Yang, W. P.; Kirchgessner, T. G. 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., 1999, 274, 37161-37168.
147. Schwarz, U. I.; Seemann, D.; Oertel, R.; Miehlke, S.; Kuhlisch, E.; Fromm, M. F.; Kim, R. B.; Bailey, D. G.; Kirch, W. Grapefruit juice ingestion significantly reduces talinolol bioavailability. Clin. Pharmacol. Ther., 2005, 77, 291-301. (Pubitemid 40470385)
148. Lee, W.; Glaeser, H.; Smith, L. H.; Roberts, R. L.; Moeckel, G. W.; Gervasini, G.; Leake, B. F.; Kim, R. B. Polymorphisms in human organic anion-transporting polypeptide 1A2 (OATP1A2): implications for altered drug disposition and central nervous system drug entry. J. Biol. Chem., 2005, 280, 9610-9617. (Pubitemid 40409657)
149. Bailey, D. G.; Dresser, G. K.; Leake, B. F.; Kim, R. B. Naringin is a major and selective clinical inhibitor of organic anion-transporting polypeptide 1A2 (OATP1A2) in grapefruit juice. Clin. Pharmacol. Ther., 2007, 81, 495-502. (Pubitemid 46452308)
150. Dresser, G. K.; Kim, R. B.; Bailey, D. G. Effect of grapefruit juice volume on the reduction of fexofenadine bioavailability: possible role of organic anion transporting polypeptides. Clin. Pharmacol. Ther., 2005, 77, 170-177. (Pubitemid 40269132)
151. Shirasaka, Y.; Kuraoka, E.; Spahn-Langguth, H.; Nakanishi, T.; Langguth, P.; Tamai, I. Species difference in the effect of grapefruit juice on intestinal absorption of talinolol between human and rat. J. Pharmacol. Exp. Ther., 2010, 332, 181-189.
152. Halestrap, A. P.; Meredith, D. The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflügers. Archiv. Eur. J. Physiol., 2004, 447, 619-628. (Pubitemid 38241446)
153. Halestrap, A. P.; Price, N. T. The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochem. J., 1999, 343, 281-299. (Pubitemid 29511759)
154. Poole, R. C.; Sansom, C. E.; Halestrap, A. P. Studies of the membrane topology of the rat erythrocyte H+/lactate cotransporter (MCT1). Biochem. J., 1996, 320, 817-824. (Pubitemid 27013796)
155. Gill, R. K.; Saksena, S.; Alrefai, W. A.; Sarwar, Z.; Goldstein, J. L.; Carroll, R. E.; Ramaswamy, K.; Dudeja, P. K. Expression and membrane localization of MCT isoforms along the length of the human intestine. Am. J. Physiol. Cell Physiol., 2005, 289, C846-852. (Pubitemid 41361640)
156. Cummings, J. H.; Macfarlane, G. T. The control and consequences of bacterial fermentation in the human colon. J. Appl. Bacteriol., 1991, 70, 443-459.
157. Juel, C. Lactate-proton cotransport in skeletal muscle. Physiol. Rev., 1997, 77, 321-358. (Pubitemid 27184342)
158. Abramson, J.; Smirnova, I.; Kasho, V.; Verner, G.; Kaback, H., R; Iwata, S. Structure and mechanism of the lactose permease of Es-cherichia. coli. Science, 2003, 301, 610-615.
159. Huang, Y.; Lemieux, M. J.; Song, J.; Auer, M.; Wang, D.-N. Structure and Mechanism of the Glycerol-3-Phosphate Transporter from Escherichia coli. Science., 2003, 301, 616-620. (Pubitemid 36927940)
160. Manoharan, C; Wilson, M. C.; Sessions, R. B.; Halestrap, A. P. The role of charged residues in the transmembrane helices of monocar-boxylate transporter 1 and its ancillary protein basigin in determining plasma membrane expression and catalytic activity. Mol. Membr. Biol., 2006, 23.
161. Wilson, M. C.; Meredith, D.; Bunnun, C; Sessions, R. B.; Halestrap, A. P. Studies on the DIDS-binding Site of Monocarboxylate Transporter 1 Suggest a Homology Model of the Open Conformation and a Plausible Translocation Cycle. J. Biol. Chem., 2009, 284., 20011-20021.
162. Law, C. J.; Maloney, P. C.; Wang, D.-N. Ins and Outs of Major Facilitator Superfamily Antiporters. Ann. Rev. Microbiol, 2008, 62, 289-305.
163. Wilson, M. C.; Meredith, D.; Fox, J. E. M.; Manoharan, C; Davies, A. J.; Halestrap, A. P. Basigin (CD147) Is the Target for Organo-mercurial Inhibition of Monocarboxylate Transporter Isoforms 1 and 4: The ancillary protein for the pCMBS insensitive MCT2 is embigin (gp70). J. Biol. Chem., 2005, 280, 27213-27221. (Pubitemid 41040760)
164. Kirk, P.; Wilson, M. C.; Heddle, C; Brown, M. H.; Barclay, A. N.; Halestrap, A. P. CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression. EMBO. J., 2000, 3896-3904. (Pubitemid 30608530)
165. Poole, R. C.; Halestrap, A. P. Transport of lactate and other mono-carboxylates across mammalian plasma membranes. Am. J. Physiol, 1993, 264, C761-C782. (Pubitemid 23118095)
166. Enerson, B. E.; Drewes, L. R. Molecular features, regulation, and function of monocarboxylate transporters: implications for drug delivery. J. Pharm. Sci., 2003, 92, 1531-1544. (Pubitemid 36929674)
167. Lam, W. K.; Felmlee, M. A.; Morris, M. E. Monocarboxylate Transporter-Mediated Transport of Î-Hydroxybutyric Acid in Human Intestinal Caco-2 Cells. Drug Metab. Disposition, 2010, 38, 441-447.
168. 2-Lactam Prodrug: Uptake and Transport of Carindacillin in Caco-2 Cells. J. Pharmacol. Exp. Ther., 1999, 290, 958-964. (Pubitemid 29400231)
169. Cundy, K. C.; Branch, R.; Chernov-Rogan, T.; Dias, T.; Estrada, T.o.; Hold, K.; Koller, K.; Liu, X.; Mann, A.; Panuwat, M.; Rail-lard, S. P.; Upadhyay, S.; Wu, Q. Q.; Xiang, J.-N.; Yan, H.; Zerangue, N.; Zhou, C. X.; Barrett, R. W.; Gallop, M. A. XP13512 [(±)-1 - ([(a-Isobutanoyloxyethoxy) carbonyl] aminomethyl)-1-cyclohexane Acetic Acid], A Novel Gabapentin Prodrug: I. Design, Synthesis, Enzymatic Conversion to Gabapentin, and Transport by Intestinal Solute Transporters J. Pharmacol. Exp. Ther., 2004, 311, 315-323. (Pubitemid 39287811)
170. Garanero, G.; Ramanathan, S.; Amidon, G. In Drug Bioavailability:. Estimation. of. Solubility,. Permeability,. Absorption. and. Bioavailability, H. van de Waterbeemd; H. Lennernas; P. Arturs-son, eds.; WILEY-VCH: Zurich., 2005; Vol. 18, pp. 191-210.
171. Balimane, P.; Sinko, P. Effect of ionization on the variable uptake of valacyclovir via the human intestinal peptide transporter (hPepT1) in CHO cells. Biopharm. Drug Dispos., 2000, 21, 165-174. (Pubitemid 32115041)
172. Giacomini, K. M.; Huang, S. M.; Tweedie, D. J.; Benet, L. Z.; Brou-wer, K. L.; Chu, X.; Dahlin, A.; Evers, R.; Fischer, V.; Hillgren, K. M.; Hoffmaster, K. A.; Ishikawa, T.; Keppler, D.; Kim, R. B.; Lee, C. A.; Niemi, M.; Polli, J. W.; Sugiyama, Y.; Swaan, P. W.; Ware, J. A.; Wright, S. H.; Yee, S. W.; Zamek-Gliszczynski, M. J.; Zhang, L. Membrane transporters in drug development. Nat. Rev. Drug Discov., 2010, 9, 215-236.
173. Klaassen, CD.; Aleksunes, L. M. Xenobiotic, bile acid, and cholesterol transporters: function and regulation. Pharmacol. Rev., 2010, 62, 1-96.
174. Murakami, T.; Takano, M. Intestinal efflux transporters and drug absorption. Expert. Opin. Drug Metab. Toxicol, 2008, 4, 923-939.