Intestinal efflux transporters and drug absorption

Expert Opinion on Drug Metabolism and Toxicology

Volumn 4, Issue 7, 2008, Pages 923-939

  Murakami, Teruo ^a   Takano, Mikihisa ^a  

^a HIROSHIMA INTERNATIONAL UNIVERSITY   (Japan)

Author keywords

ABC efflux transporters; Biopharmaceutics Classification System (BCS); Breast cancer resistance protein; Multi drug resistance associated proteins; Oral bioavailability; P Glycoprotein

Indexed keywords

ABC TRANSPORTER; BREAST CANCER RESISTANCE PROTEIN; CARBAMAZEPINE; CIPROFLOXACIN; CYCLOSPORIN; CYCLOSPORIN A; DAUNORUBICIN; DEXAMETHASONE; DIGOXIN; ELACRIDAR; FEXOFENADINE; GLYCOPROTEIN P; IRINOTECAN; IVERMECTIN; KETOCONAZOLE; LOPERAMIDE; METHOTREXATE; MULTIDRUG RESISTANCE PROTEIN 2; MULTIDRUG RESISTANCE PROTEIN 3; PACLITAXEL; PANTOPRAZOLE; QUINIDINE; RIFAMPICIN; RITONAVIR; SALAZOSULFAPYRIDINE; TACROLIMUS; TALINOLOL; UNINDEXED DRUG; VERAPAMIL; VINBLASTINE;

AREA UNDER THE CURVE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG DOSAGE FORM COMPARISON; DRUG FORMULATION; DRUG MECHANISM; DRUG PENETRATION; DRUG POTENTIATION; DRUG SOLUBILITY; DRUG TRANSPORT; ENZYME SPECIFICITY; ENZYME SUBSTRATE; FOOD; FOOD DRUG INTERACTION; GENETIC POLYMORPHISM; GRAPEFRUIT; HUMAN; INTESTINE ABSORPTION; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN STRUCTURE; REVIEW; TISSUE DISTRIBUTION;

ANIMALS; ATP-BINDING CASSETTE TRANSPORTERS; CARRIER PROTEINS; ENTEROCYTES; HUMANS; INTESTINAL ABSORPTION; INTESTINES; PHARMACEUTICAL PREPARATIONS; SOLUBILITY;

EID: 49649120671     PISSN: 17425255     EISSN: None     Source Type: Journal    
DOI: 10.1517/17425255.4.7.923     Document Type: Review

References (115)

1. Takano M, Yumoto R, Murakami T. Expression and function of efflux drug transporters in the intestine. Pharmacol Ther 2006;109:137-61
2. Mizuno N, Niwa T, Yotsumoto Y, Sugiyama Y. Impact of drug transporter studies on drug discovery and development. Pharmacol Rev 2003;55:425-61
3. Chan LMS, Lowes S, Hirst BH. The ABCs of drug transport in intestine and liver: efflux proteins limiting drug absorption and bioavailability. Eur J Pharm Sci 2004;21:25-51
4. Suzuki H, Sugiyama Y. Single nucleotide polymorphisms in multidrug resistance associated protein 2 (MRP2/ABCC2): its impact on drug disposition. Adv Drug Deliv Rev 2002;54:1311-31
5. Doyle LA, Ross DD. Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2). Oncogene 2003;22:7340-58
6. Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 1995;12:413-20
7. Wu CY, Benet LZ. 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
8. Ling V, Thompson LH. Reduced permeability in CHO cells as a mechanism of resistance to colchicine. J Cell Physiol 1974;83:103-16
9. Juliano RL, Ling V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 1976;455:152-62
10. Fojo AT, Ueda K, Slamon DJ, et al. Expression of a multidrug-resistance gene in human tumors and tissues. Proc Natl Acad Sci USA 1987;84:265-9
11. Chen CJ, Chin JE, Ueda K, et al. Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell 1986;7:381-9
12. Ho GT, Moodlie FM, Satsangi J. Multidrug resistance 1 gene (P-glycoprotein 170): an important determinant in gastrointestinal disesse? Gut 2003;52:759-66
13. Mouly S, Paine MF. P-glycoprotein increases from proximal to distal regions of human small intestine. Pharm Res 2003;20:1595-9
14. Von Richter O, Burk O, Fromm MF, et al. Cytochrome P450 3A4 and P-glycoprotein expression in human small intestinal enterocytes and hepatocytes: a comparative analysis in paired tissue specimens. Clin Pharmacol Ther 2004;75:172-83
15. Makhey VD, Guo A, Norris DA, et al. Characterization of the regional intestinal kinetics of drug efflux in rat and human intestine and in Caco-2 cells. Pharm Res 1998;15:1160-7
16. Yumoto R, Murakami T, Nakamoto Y, et al. Transport of rhodamine 123, a P-glycoprotein substrate, across rat intestine and Caco-2 cell monolayers in the presence of cytochrome P450 3A-related compounds. J Pharmacol Exp Ther 1999;289:149-55
17. Stephens RH, O'Nell, Warhurst A, et al. Kinetic profiling of P-glycoprotein-mediated drug efflux in rat and human intestinal epithelia. J Pharmacol Exp Ther 2001;296:584-91
18. Chen C, Liu X, Smith BJ. Utility of Mdr1-gene deficient mice in assessing the impact of P-glycoprotein on pharmacokinetics and pharmacodynamics in drug discovery and development. Curr Drug Metab 2003;4:272-91
19. Tammur J, Prades C, Arnould I, et al. Two new genes from the human ATP-binding cassette transporter superfamily, ABCC11 and ABCC12, tandemly duplicated on chromosome 16q12. Gene 2001;273:89-96
20. Hopper E, Belinsky MG, Zeng H, et al. Analysis of the structure and expression pattern of MRP7 (ABCC10), a new member of the MRP subfamily. Cancer Lett 2001;162:181-91
21. Prime-Chapman HM, Fearn RA, Cooper AE, et al. Differential multidrug resistance-associated protein 1 through 6 isoform expression and function in human intestinal epithelial Caco-2 cells. J Pharmacol Exp Ther 2004;311:476-84
22. Johnson BM, Zhang P, Schuetz JD, Brouwer KL. Characterization of transport protein expression in multidrug resistance-associated protein (Mrp) 2-deficient rats. Drug Metab Dispos 2006;34:556-62
23. Maher JM, Cerrington NJ, Slitt AL, Klaassen CD. Tissue distribution and induction of the rat multidrug resistance-associated proteins 5 and 6. Life Sci 2006;78:2219-25
24. Hilgendorf C, Ahlin G, Seithel A, et al. Expression of thirty-six drug transporter genes in human intestine, liver, kidney, and organotypic cell lines. Drug Metab Dispos 2007;35:1333-40
25. Rost D, Mahner S, Sugiyama Y, Stremmel W. Expression and localization of the multidrug resistance-associated protein 3 in rat small and large intestine. Am J Physiol Gastrointest Liver Physiol 2002;282:G720-6
26. Zhang DW, Gu HM, Vasa M, et al. Characterization of the role of polar amino acid residues within predicted transmembrane helix 17 in determining the substrate specificity of multidrug resistance protein 3. Biochemistry 2003;42:9989-10000
27. Jansen PL, Van Klinken JW, Van Gelder M, et al. Preserved organic anion transport in mutant TR- rats with a hepatobiliary secretion defect. Am J Physiol 1993;265:G445-52
28. Hosokawa S, Tagaya O, Mikami T, et al. A new rat mutant with chronic conjugated hyperbilirubinemia and renal glomerular lesions. Lab Anim Sci 1992;42:27-34
29. Jansen PL, Peters WH, Lamers WH. Hereditary chronic conjugated hyperbilirubinemia in mutant rats caused by defective hepatic anion transport. Hepatology 1985;5:573-9
30. Chu XY, Strauss JR, Mariano MA, et al. Characterization of mice lacking the multidrug resistance protein MRP2 (ABCC2). J Pharmacol Exp Ther 2006;317:579-89
31. Nies AT, Keppler D. The apical conjugate efflux pump ABCC2 (MRP2). Pflugers Arch 2007;453:643-59
32. König J, Rost D, Cui Y, Keppler D. Characterization of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrane. Hepatology 1999;29:1156-63
33. Yokooji T, Murakami T, Yumoto R, et al. Site-specific bidirectional efflux of 2,4-dinitrophenyl-S-glutathione, a substrate of multidrug resistance-associated proteins, in rat intestine and Caco-2 cells. J Pharm Pharmacol 2007;59:513-20
34. Taipalensuu J, Tomblom H, Lindberg G, et al. 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 monolayers. J Pharmacol Exp Ther 2001;299:164-70
35. Englund G, Rorsman F, Rönnblom A, et al. 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;29:269-77
36. Seithel A, Karlsson J, Hilgendorf C, et al. Variability in mRNA expression of ABC- and SLC-transporters in human intestinal cells: comparison between human segments and Caco-2 cells. Eur J Pharm Sci 2006;28:291-9
37. Berggren S, Gall C, Wollnitz N, Ekelund M, et al. Gene and protein expression of P-glycoprotein, MRP1, MRP2, and CYP3A4 in the small and large human intestine. Mol Pharm 2007;4:252-7
38. Hirohashi T, Suzuki H, Takikawa H, Sugiyama Y. ATP-dependent transport of bile salts by rat multidrug resistance-associated protein 3 (Mrp3). J Biol Chem 2000;275:2905-10
39. Akita H, Suzuki H, Hirohashi T, et al. Transport activity of human MRP3 expressed in Sf9 cells: comparative studies with rat MRP3. Pharm Res 2002;19:34-41
40. Kuroda M, Kobayashi Y, Tanaka Y, et al. Increased hepatic and renal expressions of multidrug resistance-associated protein 3 in Eisai hyperbilirubinuria rats. J Gastroenterol Hepatol 2004;19:146-53
41. Zelcer N, Van De Wetering K, De Waart R, et al. Mice lacking Mrp3 (Abcc3) have normal bile salt transport, but altered hepatic transport of endogenous glucuronides. J Hepatol 2006;44:768-75
42. Doyle LA, Yang W, Abruzzo LV, et al. A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci USA 1998;95:15665-70
43. Allikmets R, Schriml LM, Hutchinson A, et al. A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance. Cancer Res 1998;58:5337-9
44. Miyake K, Mickley L, Litman T, et al. Molecular cloning of cDNAs which are highly overexpressed in mitoxantrone-resistant cells: demonstration of homology to ABC transport genes. Cancer Res 1999;59:8-13
45. Staud F, Pavek P. Breast cancer resistance protein (BCRP/ABCG2). Int J Biochem Cell Biol 2005;37:720-5
46. Maliepaard M, Scheffer GL, Faneyte IF, et al. Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues. Cancer Res 2001;61:3458-64
47. Huls M, Brown CD, Windass AS, et al. The breast cancer resistance protein transporter ABCG2 is expressed in the human kidney proximal tubule apical membrane. Kidney Int 2008;73:220-5
48. Enokizono J, Kusuhara H, Sugiyama Y. Regional expression and activity of breast cancer resistance protein (Bcrp/Abcg2) in mouse intestine: overlapping distribution with sulfotransferases. Drug Metab Dispos 2007;35:922-8
49. Mao Q, Unadkat JD. Role of the breast cancer resistance protein (ABCG2) in drug transport. AAPS J 2005;7:E118-33
50. Wu C-Y, Benet LZ, Hebert MF, et al. Differentiation of absorption and first-pass gut and hepatic metabolism in humans: studies with cyclosporine. Clin Pharmacol Ther 1995;58:492-7
51. Komura H, Iwaki M. Species differences in in vitro and in vivo small intestinal metabolism of CYP3A substrates. J Pharm Sci 2007;97:1775-800
52. Ducharme MP, Warbasse LH, Edwards DJ. Disposition of intravenous and oral cyclosporine after administration with grapefruit juice. Clin Pharmacol Ther 1995;57:485-91
53. Kato M, Chiba K, Hisaka A, et al. The intestinal first-pass metabolism of substrates of CYP3A4 and P-glycoprotein - quantitative analysis based on information from the literature. Drug Metab Pharmacokin 2003;18:365-72
54. Masuda S, Uemoto S, Goto M, et al. Tacrolimus therapy according to mucosal MDR1 levels in small-bowel transplant recipients. Clin Pharmacol Ther 2004;75:352-61
55. Masuda S, Inui K. An up-date review an individualized dosage adjustment of calcineurin inhibitors in organ transplant patients. Pharmacol Ther 2006;112:184-98
56. Bernsdorf A, Giessmann T, Modess C, et al. Simvastatin does not influence the intestinal P-glycoprotein and MPR2, and the disposition of talinolol after chronic medication in healthy subjects genotyped for the ABCB1, ABCC2 and SLCO1B1 polymorphisms. Br J Clin Pharmacol 2006;61:440-50
57. Siegmund W, Ludwig K, Engel G, et al. Variability of intestinal expression of P-glycoprotein in healthy volunteers as described by absorption of talinolol from four bioequivalent tablets. J Pharm Sci 2003;92:604-10
58. Tamura S, Tokunaga Y, Ibuki R, et al. The site-specific transport and metabolism of tacrolimus in rat small intestine. J Pharmacol Exp Ther 2003;306:310-6
59. Jin M, Shimada T, Shintani M, et al. Long-term levothyroxine treatment decreases the oral bioavailability of cyclosporin A by inducing P-glycoprotein in small intestine. Drug Metab Pharmacokinet 2005;20:324-30
60. Schwarz UI, Hanso H, Oertel R, et al. Induction of intestinal P-glycoprotein by St John's wort reduces the oral bioavailability of talinolol. Chin Pharmacol Ther 2007;81:669-78
61. Giessmann T, May K, Modess C, et al. Carbamazepine regulates intestinal P-glycoprotein and multidrug resistance protein MRP2 and influences disposition of talinolol in humans. Clin Pharmacol Ther 2004;76:192-200
62. Westphal K, Weinbrenner A, Zschiesche M, et al. 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;68:345-55
63. Li D, Gui R, Li J, et al. Tacrolimus dosing in Chinese renal transplant patients is related to MDR1 gene C3435T polymorphisms. Transplant Proc 2006;38:2850-2
64. Buchman AL, Paine MF, Wallin A, Ludington SS. A higher dose requirement of tacrolimus in active Crohn's disease may be related to a high intestinal P-glycoprotein content. Dig Dis Sci 2005;50:2312-5
65. Lemahieu WP, Maes BD, Verbeke K, Vanrenterghem Y. CYP3A4 and P-glycoprotein activity in healthy controls and transplant patients on cyclosporin vs. tacrolimus vs. sirolimus. Am J Transplant 2004;4:1514-22
66. Foote CJ, Greer W, Kiberd BA, et al. MDR1 C3435T polymorphisms correlate with cyclosporine levels in de novo renal recipients. Transplant Proc 2006;38:2847-9
67. Masuda S, Goto M, Kiuchi T, et al. Enhanced expression of enterocyte P-glycoprotein depresses cyclosporine bioavailability in a recipient of living donor liver transplantation. Liver Transpl 2003;9:1108-13
68. Huang ZH, Murakami T, Okochi A, et al. Expression and function of P-glycoprotein in rats with carbon tetrachloride-induced acute hepatic failure. J Pharm Pharmacol 2001;53:873-81
69. Yumoto R, Murakami T, Takano M. Differential effect of acute hepatic failure on in vivo and in vitro P-glycoprotein functions in the intestine. Pharm Res 2003;20:765-71
70. Huang ZH, Murakami T, Okochi A, et al. Expression and function of P-glycoprotein in rats with glycerol-induced acute renal failure. Eur J Pharmacol 2000;406:453-60
71. Murakami T, Yumoto R, Nagai J, Takano M. Factors affecting the expression and function of P-glycoprotein in rats: drug treatments and diseased states. Pharmazie 2002;57:102-7
72. Murakami T, Fukuda T, Yumoto R, et al. Interaction of endogenous compounds in human and rat urine with P-glycoprotein. Drug Metab Pharmacokinet 2002;17:245-52
73. Gotoh Y, Suzuki H, Kinoshita S, et al. Involvement of an organic anion transporter (canalicular multispecific organic anion transporter/ multidrug resistance-associated protein 2) in gastrointestinal secretion of glutathione conjugates in rats. J Pharmacol Exp Ther 2000;292:433-9
74. Yokooji T, Murakami T, Yumoto R, et al. Function of multidrug resistance-associated protein 2 in acute hepatic failure rats. Eur J Pharmacol 2006;546:152-60
75. Yokooji T, Murakami T, Yumoto R, et al. Role of intestinal efflux transporters in the intestinal absorption of methotrexate in rats. J Pharm Pharmacol 2007;59:1263-70
76. Kruijtzer CM, Beijnen JH, Rosing H, et al. Increased oral bioavailability of topotecan in combination with the breast cancer resistance protein and P-glycoprotein inhibitor GF120918. J Clin Oncol 2002;20:2943-50
77. Sparreboom A, Loos WJ, Burger H, et al. Effect of ABCG2 genotype on the oral bioavailability of topotecan. Cancer Biol Ther 2005;4:650-8
78. Zhang W, Yu BN, He YJ, et al. Role of BCRP 421C>A polymorphism on rosuvastatin pharmacokinetics in healthy Chinese males. Clin Chim Acta 2006;373:99-103
79. Yamasaki Y, Ieiri I, Kusuhara H, et al. Pharmacogenetic characterization of sulfasalazine disposition based on NAT2 and ABCG2 BCRP) gene polymorphisms in humans. Clin Pharmacol Ther 2008 [Epub ahead of print]
80. Jonker JW, Smit JW, Brinkhuis RF, et al. Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan. J Natl Cancer Inst 2000;92:1651-6
81. Zaher H, Khan AA, Palandra J, et al. Breast cancer resistance protein (Bcrp/abcg2) is a major determinant of sulfasalazine absorption and elimination in the mouse. Mol Pharm 2006;3:55-61
82. Merino G, Alvarez AI, Pulido MM, et al. Breast cancer resistance protein (BCRP/ABCG2) transports fluoroquinolone antibiotics and affects their oral availability, pharmacokinetics, and milk secretion. Drug Metab Dispos 2006;34:690-5
83. Van Herwaarden AE, Wagenaar E, Karnekamp B, et al. Breast cancer resistance protein (Bcrp1/Abcg2) reduces systemic exposure of the dietary carcinogens aflatoxin B1, IQ and Trp-P-1 but also mediates their secretion into breast milk. Carcinogenesis 2006;27:123-30
84. Van Herwaarden AE, Jonker JW, Wagenaar E, et al. The breast cancer resistance protein (Bcrp1/Abcg2) restricts exposure to the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine. Cancer Res 2003;63:6447-52
85. Chen C, Mireles RJ, Campbell SD, et al. Differential interaction of 3-hydroxy-3-methylglutaryl-coa reductase inhibitors with ABCB1, ABCC2, and OATP1B1. Drug Metab Dispos 2005;33:537-46
86. Hirano M, Maeda K, Matsushima S, et al. Involvement of BCRP (ABCG2) in the biliary excretion of pitavastatin. Mol Pharmacol 2005;68:800-7
87. Guo A, Marinaro W, Hu P, Sinko PJ. Delineating the contribution of secretory transporters in the efflux of etoposide using Madin-Darby canine kidney (MDCK) cells overexpressing P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP1), and canalicular multispecific organic anion transporter (cMOAT). Drug Metab Dispos 2002;30:457-63
88. Aiien JD, Van Dort SC, Buitelaar M, et al. Mouse breast cancer resistance protein (Bcrp1/Abcg2) mediates etoposide resistance and transport, but etoposide oral availability is limited primarily by P-glycoprotein. Cancer Res 2003;63:1339-44
89. Badagnani I, Castro PA, Taylor TR, et al. Interaction of methotrexate with organic-anion transporting polypeptide 1A2 and its genetic variants. J Pharmacol Exp Ther 2006;318:521-9
90. El-Sheikh AA, Van Den Heuvel JJ, Koenderink JB, Russel FG. Interaction of nonsteroidal anti-inflammatory drugs with multidrug resistance protein (MRP) 2/ABCC2- and MRP4/ABCC4-mediated methotrexate transport. J Pharmacol Exp Ther 2007;320:229-35
91. Breedveld P, Plium D, Cipriani G, et al. The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models. Mol Pharmacol 2007;71:240-9
92. +-oligopeptide cotransporter hPEPT1. J Physiol 2006; 574:149-66
93. Yao HM, Chiou WL. The complexity of intestinal absorption and exsorption of digoxin in rats. Int J Pharm 2006;322:79-86
94. Cao X, Yu LX, Barbaciru C, et al. Permeability dominates in vivo intestinal absorption of P-gp substrate with high solubility and high permeability. Mol Pharm 2005;2:329-40
95. Ogihara T, Kamiya M, Ozawa M, et al. What kinds of substrates show P-glycoprotein-dependent intestinal absorption? Comparison of verapamil with vinblastine. Drug Metab Pharmacokinet 2006;21:238-44
96. Adachi Y, Suzuki H, Sugiyama Y. Quantitative evaluation of the function of small intestinal P-glycoprotein: comparative studies between in situ and in vitro. Pharm Res 2003;20:1163-9
97. Drescher S, Glaeserh, Mürdter T, et al. P-glycoprotein-mediated intestinal and biliary digoxin transport in humans. Clin Pharmacol Ther 2003;73:223-31
98. Mori N, Yokooji T, Murakami T. Fate of quinidine, a P-glycoprotein substrate, in the gastrointestinal tract after oral administration in rats. Pharmazie 2008;63:241-4
99. Tubic M, Wagner D, Spahn-Langguth H, et al. Effects of controlled-release on the pharmacokinetics and absorption characteristics of a compound undergoing intestinal efflux in humans. Eur J Pharm Sci 2006;29:231-9
100. Van Mourik IDM, Thomson M, Kelly DA. Comparison of pharmacokinetics of Neoral and Sandimmune in stable pediatric liver transplant recipients. Liver Transpl Surg 1999;5:107-11
101. Fujino H, Saito T, Ogawa S, Kojima J. Transporter-mediated influx and efflux mechanisms of pitavastatin, a new inhibitor of HMG-CoA reductase. J Pharm Pharmacol 2005;57:1305-11
102. Jain R, Duvvuri S, Kansara V, et al. Intestinal absorption of novel-dipeptide prodrugs of saquinavir in rats. Int J Pharm 2007;336:233-40
103. Funakoshi S, Murakami T, Yumoto R, et al. Role of P-glycoprotein in pharmacokinetics and drug interactions of digoxin and beta-methyldigoxin in rats. J Pharm Sci 2003;92:1455-63
104. Pauli-Magnus C, Mürdter T, Godel A, et al. P-glycoprotein-mediated transport of digitoxin, alpha-methyldigoxin and beta-acetyldigoxin. Naunyn Schmiedebergs Arch Pharmacol 2001;363:337-43
105. Das G. Beta-methyl digoxin: a better absorbable digoxin. Int J Clin Pharmacol Ther Toxicol 1989;27:521-5
106. Shono Y, Nishihara H, Matsuda Y, et al. Modulation of intestinal P-glycoprotein function by cremophor EL and other surfactants by an in vitro diffusion chamber method using the isolated rat intestinal membranes. J Pharm Sci 2004;93:877-85
107. Yamagata T, Kusuhara H, Morishita M, et al. 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;35:1142-8
108. Arima H, Yunomae K, Hirayama F, Uekama K. Contribution of P-glycoprotein to the enhancing effects of dimethyl-beta-cyclodextrin on oral bioavailability of tacrolimus. J Pharmacol Exp Ther 2001;297:547-55
109. Sakai M, Hobaro N, Hokama N, et al. Increased bioavailability of tacrolimus after rectal administration in rats. Biol Pharm Bull 2004;27:1480-2
110. Englund G, Jacobson A, Rorsman F, et al. Efflux transporters in ulcerative colitis: decreased expression of BCRP (ABCG2) and Pgp (ABCB1). Inflamm Bowel Dis 2007;13:291-7
111. Langmann T, Moehle C, Mauerer R, et al. Loss of detoxification in inflammatory bowel disease: dysregulation of pregnane X receptor target genes. Gastroenterology 2004;127:26-40
112. Maezono S, Sugimoto K, Sakamota K, et al. Elevated blood concentrations of calcineurin inhibitors during diarrheal episode in pediatric liver transplant recipients: involvement of the suppression of intestinal cytochrome P450 3A and P-glycoprotein. Pediatr Transplant 2005;9:315-23
113. Sun H, Frassetto L, Benet LZ. Effects of renal failure on drug transport and metabolism. Pharmacol Ther 2006;109:1-11
114. Naud J, Michaud J, Boisvert C, et al. Down-regulation of intestinal drug transporters in chronic renal failure in rats. J Pharmacol Exp Ther 2007;320:978-85
115. Lemahieu WP, Maes BD, Verbeke K, Vanrenterghem Y. Alterations of CYP3A4 and P-glycoprotein activity in vivo with time in renal graft recipients. Kidney Int 2004;66:433-40