In vivo probes of drug transport: Commonly used probe drugs to assess function of intestinal P-glycoprotein (ABCB1) in humans

Handbook of Experimental Pharmacology

Volumn 201, Issue , 2011, Pages 403-447

  Oswald, Stefan ^a   Terhaag, Bernd ^b   Siegmund, Werner ^a  

^a UNIVERSITY OF GREIFSWALD   (Germany)

^b AWDpharma GmbH and Co KG   (Germany)

Author keywords

ABCB1; Digoxin; Intestinal absorption; P glycoprotein; Talinolol

Indexed keywords

ALPHA TOCOPHEROL SUCCINATE; AMIODARONE; CARBAMAZEPINE; CARVEDILOL; CLARITHROMYCIN; COLCHICINE; CYCLOSPORIN; DEXAMETHASONE; DIGOXIN; ERYTHROMYCIN; GINKGO BILOBA EXTRACT; HYPERICUM PERFORATUM EXTRACT; ITRACONAZOLE; LEVOTHYROXINE; METOCLOPRAMIDE; MULTIDRUG RESISTANCE PROTEIN 1; PLACEBO; PRAVASTATIN; PRAZOSIN; PROPANTHELINE BROMIDE; QUINIDINE; RIFAMPICIN; RITONAVIR; SCHISANDRA CHINENSIS EXTRACT; SILYMARIN; TALINOLOL; UNINDEXED DRUG; VALSPODAR; VERAPAMIL; VINBLASTINE;

ABSENCE OF SIDE EFFECTS; AREA UNDER THE CURVE; CENTRAL NERVOUS SYSTEM DISEASE; DOSAGE SCHEDULE COMPARISON; DOSE RESPONSE; DRUG ABSORPTION; DRUG ACCUMULATION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG COMPETITION; DRUG DISPOSITION; DRUG DISTRIBUTION; DRUG DOSE ESCALATION; DRUG ELIMINATION; DRUG EXCRETION; DRUG EXPOSURE; DRUG HALF LIFE; DRUG INHIBITION; DRUG METABOLISM; DRUG PENETRATION; DRUG SAFETY; DRUG TOLERABILITY; DRUG TRANSFORMATION; DRUG TRANSPORT; FOOD; FOOD DRUG INTERACTION; GENETIC POLYMORPHISM; GRAPEFRUIT JUICE; HEART ARRHYTHMIA; HEART ATRIUM FIBRILLATION; HEART FAILURE; HUMAN; HYPERTENSION; HYPOTHYROIDISM; IN VIVO STUDY; INTESTINE ABSORPTION; ISCHEMIC HEART DISEASE; LOW DRUG DOSE; MAXIMUM PLASMA CONCENTRATION; MEAN RESIDENCE TIME; MULTIPLE DRUG DOSE; NAUSEA AND VOMITING; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INDUCTION; REPEATED DRUG DOSE; REVIEW; SINGLE DRUG DOSE; STEADY STATE; TIME TO MAXIMUM PLASMA CONCENTRATION; UNSPECIFIED SIDE EFFECT;

ANIMALS; BIOLOGICAL TRANSPORT; DIGOXIN; HUMANS; INTESTINES; MOLECULAR PROBE TECHNIQUES; MOLECULAR PROBES; P-GLYCOPROTEIN; PROPANOLAMINES; REPRODUCIBILITY OF RESULTS;

EID: 78649653591     PISSN: 01712004     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-3-642-14541-4_11     Document Type: Review

References (212)

1. Aarnoudse AJ, Dieleman JP, Visser LE, Arp PP, van der Heiden I, van Schaik RH, Molokhia M, Hofman A, Uitterlinden AG, Stricker BH (2008) Common ATP-binding cassette B1 variants are associated with increased digoxin serum concentration. Pharmacogenet Genomics 18:299-305
2. Amidon GL, Lennernas H, Shah VP, Crison JR (1995) A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 12:413-420
3. Aronson JK (1980) Clinical pharmacokinetics of digoxin 1980. Clin Pharmacokinet 5:137-149
4. Atkinson HC, Begg EJ (1988) Relationship between human milk lipid-ultrafiltrate and octanolwater partition coefficients. J Pharm Sci 77:796-798
5. Bailey DG, Dresser GK, Leake BF, Kim RB (2007) Naringin is a major and selective clinical inhibitor of organic anion-transporting polypeptide 1A2 (OATP1A2) in grapefruit juice. Clin Pharmacol Ther 81:495-502
6. Baris N, Kalkan S, Guneri S, Bozdemir V, Guven H (2006) Influence of carvedilol on serum digoxin levels in heart failure: is there any gender difference? Eur J Clin Pharmacol 62:535-538
7. Bauman JL, DiDomenico RJ, Galanter WL (2006) Mechanisms, manifestations, and management of digoxin toxicity in the modern era. Am J Cardiovasc Drugs 6:77-86
8. Becquemont L, Verstuyft C, Kerb R, Brinkmann U, Lebot M, Jaillon P, Funck-Brentano C (2001) Effect of grapefruit juice on digoxin pharmacokinetics in humans. Clin Pharmacol Ther 70:311-316
9. Bernsdorf A, May K, Kunert-Keil C, Moritz KU, Kroemer HK, Siegmund W (2003) Expression of P-glycoprotein and MRP2 and distribution of talinolol in MRP2-deficient rats (GY/TR). Naunyn-Schmiedebergs Arch Pharmacol 367: R110
10. Bernsdorf A, Giessmann T, Modess C, Wegner D, Igelbrink S, Hecker U, Haenisch S, Cascorbi I, Terhaag B, Siegmund W (2006) 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 61:440-450
11. Bogman K, Zysset Y, Degen L, Hopfgartner G, Gutmann H, Alsenz J, Drewe J (2005) P-glycoprotein and surfactants: effect on intestinal talinolol absorption. Clin Pharmacol Ther 77:24-32
12. Bolger MB, Lukacova V, Woltosz WS (2009) Simulations of the nonlinear dose dependence for substrates of influx and efflux transporters in the human intestine. AAPS J 11:353-363
13. Buchman AL, Paine MF, Wallin A, Ludington SS (2005) A higher dose requirement of tacrolimus in active Crohn's disease may be related to a high intestinal P-glycoprotein content. Dig Dis Sci 50:2312-2315
14. Burk O, Arnold KA, Geick A, Tegude H, Eichelbaum M (2005) A role for constitutive androstane receptor in the regulation of human intestinal MDR1 expression. Biol Chem 386:503-513
15. Caldwell JH, Cline CT (1976) Biliary excretion of digoxin in man. Clin Pharmacol Ther 19:410-415
16. Chan LM, Lowes S, Hirst BH (2004) The ABCs of drug transport in intestine and liver: efflux proteins limiting drug absorption and bioavailability. Eur J Pharm Sci 21:25-51
17. Cisler JJ, Buchman AL (2005) Intestinal adaptation in short bowel syndrome. J Investig Med 53:402-413
18. Cleland JG, Dargie HJ, Pettigrew A, Gillen G, Robertson JI (1986) The effects of captopril on serum digoxin and urinary urea and digoxin clearances in patients with congestive heart failure. Am Heart J 112:130-135
19. Cogan JJ, Humphreys MH, Carlson CJ, Benowitz NL, Rapaport E (1981) Acute vasodilator therapy increases renal clearance of digoxin in patients with congestive heart failure. Circulation 64:973-976
20. Collett A, Tanianis-Hughes J, Carlson GL, Harwood MD, Warhurst G (2005) Comparison of P-glycoprotein-mediated drug-digoxin interactions in Caco-2 with human and rodent intestine: relevance to in vivo prediction. Eur J Pharm Sci 26:386-393
21. Comets E, Verstuyft C, Lavielle M, Jaillon P, Becquemont L, Mentre F (2007) Modelling the influence of MDR1 polymorphism on digoxin pharmacokinetic parameters. Eur J Clin Pharmacol 63:437-449
22. Cordon-Cardo C, O'Brien JP, Boccia J, Casals D, Bertino JR, Melamed MR (1990) Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumor tissues. J Histochem Cytochem 38:1277-1287
23. De Castro WV, Mertens-Talcott S, Derendorf H, Butterweck V (2007) Grapefruit juice-drug interactions: Grapefruit juice and its components inhibit P-glycoprotein (ABCB1) mediated transport of talinolol in Caco-2 cells. J Pharm Sci 96:2808-2817
24. de Castro WV, Mertens-Talcott S, Derendorf H, Butterweck V (2008) Effect of grapefruit juice, naringin, naringenin, and bergamottin on the intestinal carrier-mediated transport of talinolol in rats. J Agric Food Chem 56:4840-4845
25. de Lannoy IA, Silverman M (1992) The MDR1 gene product, P-glycoprotein, mediates the transport of the cardiac glycoside, digoxin. Biochem Biophys Res Commun 189:551-557
26. de Lannoy IA, Koren G, Klein J, Charuk J, Silverman M (1992) Cyclosporin and quinidine inhibition of renal digoxin excretion: evidence for luminal secretion of digoxin. Am J Physiol 263: F613-F622
27. De Mey C, Brendel E, Enterling D (1990) Carvedilol increases the systemic bioavailability of oral digoxin. Br J Clin Pharmacol 29:486-490
28. De Mey C, Schroeter V, Butzer R, Jahn P, Weisser K, Wetterich U, Terhaag B, Mutschler E, Spahn-Langguth H, Palm D (1995) Dose-effect and kinetic-dynamic relationships of the betaadrenoceptor blocking properties of various doses of talinolol in healthy humans. J Cardiovasc Pharmacol 26:879-888
29. Ding R, Tayrouz Y, Riedel KD, Burhenne J, Weiss J, Mikus G, Haefeli WE (2004) Substantial pharmacokinetic interaction between digoxin and ritonavir in healthy volunteers. Clin Pharmacol Ther 76:73-84
30. Dobkin JF, Saha JR, Butler VP Jr, Neu HC, Lindenbaum J (1982) Inactivation of digoxin by Eubacterium lentum, an anaerobe of the human gut flora. Trans Assoc Am Physicians 95:22-29
31. Doherty JE, Ferrell CB, Towbin EJ (1969) Localization of the renal excretion of the tritiated digoxin. Am J Med Sci 258:181-189
32. Doppenschmitt S, Spahn-Langguth H, Regardh CG, Langguth P (1998) Radioligand-binding assay employing P-glycoprotein-overexpressing cells: testing drug affinities to the secretory intestinal multidrug transporter. Pharm Res 15:1001-1006
33. Doppenschmitt S, Langguth P, Regardh CG, Andersson TB, Hilgendorf C, Spahn-Langguth H (1999) Characterization of binding properties to human P-glycoprotein: development of a [3H] verapamil radioligand-binding assay. J Pharmacol Exp Ther 288:348-357
34. Drescher S, Glaeser H, Murdter T, Hitzl M, Eichelbaum M, Fromm MF (2003) P-glycoproteinmediated intestinal and biliary digoxin transport in humans. Clin Pharmacol Ther 73:223-231
35. 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
36. Dresser GK, Schwarz UI, Wilkinson GR, Kim RB (2003) Coordinate induction of both cytochrome P4503A and MDR1 by St John's wort in healthy subjects. Clin Pharmacol Ther 73:41-50
37. Dresser GK, Kim RB, Bailey DG (2005) Effect of grapefruit juice volume on the reduction of fexofenadine bioavailability: possible role of organic anion transporting polypeptides. Clin Pharmacol Ther 77:170-177
38. Drozdowski L, Thomson AB (2006) Intestinal mucosal adaptation. World J Gastroenterol 12:4614-4627
39. Dudley AJ, Bleasby K, Brown CD (2000) The organic cation transporter OCT2 mediates the uptake of beta-adrenoceptor antagonists across the apical membrane of renal LLC-PK (1) cell monolayers. Br J Pharmacol 131:71-79
40. Durr D, Stieger B, Kullak-Ublick GA, Rentsch KM, Steinert HC, Meier PJ, Fattinger K (2000) St John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin Pharmacol Ther 68:598-604
41. Eberl S, Renner B, Neubert A, Reisig M, Bachmakov I, Konig J, Dorje F, Murdter TE, Ackermann A, Dormann H, Gassmann KG, Hahn EG, Zierhut S, Brune K, Fromm MF (2007) Role of p-glycoprotein inhibition for drug interactions: evidence from in vitro and pharmacoepidemiological studies. Clin Pharmacokinet 46:1039-1049
42. El Ela AA, Hartter S, Schmitt U, Hiemke C, Spahn-Langguth H, Langguth P (2004) Identification of P-glycoprotein substrates and inhibitors among psychoactive compounds - implications for pharmacokinetics of selected substrates. J Pharm Pharmacol 56:967-975
43. Englund G, Rorsman F, Ronnblom A, Karlbom U, Lazorova L, Grasjo J, Kindmark A, Artursson P (2006) 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 29:269-277
44. Fan L, Mao XQ, Tao GY, Wang G, Jiang F, Chen Y, Li Q, Zhang W, Lei HP, Hu DL, Huang YF, Wang D, Zhou HH (2009) Effect of Schisandra chinensis extract and Ginkgo biloba extract on the pharmacokinetics of talinolol in healthy volunteers. Xenobiotica 39:249-254
45. Fan L, Tao GY, Wang G, Chen Y, Zhang W, He YJ, Li Q, Lei HP, Jiang F, Hu DL, Huang YF, Zhou HH (2009) Effects of Ginkgo biloba extract ingestion on the pharmacokinetics of talinolol in healthy Chinese volunteers. Ann Pharmacother 43:944-949
46. Fenner KS, Troutman MD, Kempshall S, Cook JA, Ware JA, Smith DA, Lee CA (2009) Drugdrug interactions mediated through P-glycoprotein: clinical relevance and in vitro-in vivo correlation using digoxin as a probe drug. Clin Pharmacol Ther 85:173-181
47. Fromm MF, Kim RB, Stein CM, Wilkinson GR, Roden DM (1999) Inhibition of P-glycoproteinmediated drug transport: a unifying mechanism to explain the interaction between digoxin and quinidine. Circulation 99:552-557
48. Fromm MF, Kauffmann HM, Fritz P, Burk O, Kroemer HK, Warzok RW, Eichelbaum M, Siegmund W, Schrenk D (2000) The effect of rifampin treatment on intestinal expression of human MRP transporters. Am J Pathol 157:1575-1580
49. Geick A, Eichelbaum M, Burk O (2001) Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. J Biol Chem 276:14581-14587
50. Gerloff T, Schaefer M, Johne A, Oselin K, Meisel C, Cascorbi I, Roots I (2002) MDR1 genotypes do not influence the absorption of a single oral dose of 1 mg digoxin in healthy white males. Br J Clin Pharmacol 54:610-616
51. Giessmann T, May K, Modess C, Wegner D, Hecker U, Zschiesche M, Dazert P, Grube M, Schroeder E, Warzok R, Cascorbi I, Kroemer HK, Siegmund W (2004) Carbamazepine regulates intestinal P-glycoprotein and multidrug resistance protein MRP2 and influences disposition of talinolol in humans. Clin Pharmacol Ther 76:192-200
52. Giessmann T, Modess C, Hecker U, Zschiesche M, Dazert P, Kunert-Keil C, Warzok R, Engel G, Weitschies W, Cascorbi I, Kroemer HK, Siegmund W (2004) CYP2D6 genotype and induction of intestinal drug transporters by rifampin predict presystemic clearance of carvedilol in healthy subjects. Clin Pharmacol Ther 75:213-222
53. Glaeser H, Fromm MF (2008) Animal models and intestinal drug transport. Expert Opin Drug Metab Toxicol 4:347-361
54. Glaeser H, Drescher S, van der Kuip H, Behrens C, Geick A, Burk O, Dent J, Somogyi A, von Richter O, Griese EU, Eichelbaum M, Fromm MF (2002) Shed human enterocytes as a tool for the study of expression and function of intestinal drug-metabolizing enzymes and transporters. Clin Pharmacol Ther 71:131-140
55. Glaeser H, Bailey DG, Dresser GK, Gregor JC, Schwarz UI, McGrath JS, Jolicoeur E, Lee W, Leake BF, Tirona RG, Kim RB (2007) Intestinal drug transporter expression and the impact of grapefruit juice in humans. Clin Pharmacol Ther 81:362-370
56. Goto M, Masuda S, Saito H, Uemoto S, Kiuchi T, Tanaka K, Inui K (2002) C3435T polymorphism in the MDR1 gene affects the enterocyte expression level of CYP3A4 rather than Pgp in recipients of living-donor liver transplantation. Pharmacogenetics 12:451-457
57. Gramatte T, Oertel R (1999) Intestinal secretion of intravenous talinolol is inhibited by luminal R-verapamil. Clin Pharmacol Ther 66:239-245
58. Gramatte T, Oertel R, Terhaag B, Kirch W (1996) Direct demonstration of small intestinal secretion and site-dependent absorption of the beta-blocker talinolol in humans. Clin Pharmacol Ther 59:541-549
59. 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
60. Gurley BJ, Swain A, Williams DK, Barone G, Battu SK (2008) Gauging the clinical significance of P-glycoprotein-mediated herb-drug interactions: comparative effects of St. John's wort, Echinacea, clarithromycin, and rifampin on digoxin pharmacokinetics. Mol Nutr Food Res 52:772-779
61. Haenisch S, May K, Wegner D, Caliebe A, Cascorbi I, Siegmund W (2008) Influence of genetic polymorphisms on intestinal expression and rifampicin-type induction of ABCC2 and on bioavailability of talinolol. Pharmacogenet Genomics 18:357-365
62. Han Y, Guo D, Chen Y, Tan ZR, Zhou HH (2009) Effect of continuous silymarin administration on oral talinolol pharmacokinetics in healthy volunteers. Xenobiotica 39:694-699
63. Hanafy A, Langguth P, Spahn-Langguth H (2001) Pretreatment with potent P-glycoprotein ligands may increase intestinal secretion in rats. Eur J Pharm Sci 12:405-415
64. Harrison LI, Gibaldi M (1976) Pharmacokinetics of digoxin in the rat. Drug Metab Dispos 4:88-93
65. Hashimoto Y, Shibakawa K, Nakade S, Miyata Y (2008) Validation and application of a 96-well format solid-phase extraction and liquid chromatography-tandem mass spectrometry method for the quantitation of digoxin in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci 869:126-132
66. Haussermann K, Benz B, Gekeler V, Schumacher K, Eichelbaum M (1991) Effects of verapamil enantiomers and major metabolites on the cytotoxicity of vincristine and daunomycin in human lymphoma cell lines. Eur J Clin Pharmacol 40:53-59
67. Hayeshi R, Hilgendorf C, Artursson P, Augustijns P, Brodin B, Dehertogh P, Fisher K, Fossati L, Hovenkamp E, Korjamo T, Masungi C, Maubon N, Mols R, Mullertz A, Monkkonen J, O'Driscoll C, Oppers-Tiemissen HM, Ragnarsson EG, Rooseboom M, Ungell AL (2008) Comparison of drug transporter gene expression and functionality in Caco-2 cells from 10 different laboratories. Eur. J Pharm Sci 35:383-396
68. Hedman A, Angelin B, Arvidsson A, Dahlqvist R, Nilsson B (1990) Interactions in the renal and biliary elimination of digoxin: stereoselective difference between quinine and quinidine. Clin Pharmacol Ther 47:20-26
69. Hedman A, Angelin B, Arvidsson A, Beck O, Dahlqvist R, Nilsson B, Olsson M, Schenck-Gustafsson K (1991) Digoxin-verapamil interaction: reduction of biliary but not renal digoxin clearance in humans. Clin Pharmacol Ther 49:256-262
70. Hinderling PH, Hartmann D (1991) Pharmacokinetics of digoxin and main metabolites/derivatives in healthy humans. Ther Drug Monit 13:381-401
71. Ho RH, Kim RB (2005) Transporters and drug therapy: implications for drug disposition and disease. Clin Pharmacol Ther 78:260-277
72. Hoffmeyer S, Burk O, von Richter O, Arnold HP, Brockmoller J, Johne A, Cascorbi I, Gerloff T, Roots I, Eichelbaum M, Brinkmann U (2000) 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 97:3473-3478
73. Holt DW, Tucker GT, Jackson PR, Storey GC (1983) Amiodarone pharmacokinetics. Am Heart J 106:840-847
74. Hori R, Okamura N, Aiba T, Tanigawara Y (1993) Role of P-glycoprotein in renal tubular secretion of digoxin in the isolated perfused rat kidney. J Pharmacol Exp Ther 266:1620-1625
75. Hosohata K, Masuda S, Yonezawa A, Katsura T, Oike F, Ogura Y, Takada Y, Egawa H, Uemoto S, Inui K (2009) MDR1 haplotypes conferring an increased expression of intestinal CYP3A4 rather than MDR1 in female living-donor liver transplant patients. Pharm Res 26:1590-1595
76. Igel S, Drescher S, Murdter T, Hofmann U, Heinkele G, Tegude H, Glaeser H, Brenner SS, Somogyi AA, Omari T, Schafer C, Eichelbaum M, Fromm MF (2007) Increased absorption of digoxin from the human jejunum due to inhibition of intestinal transporter-mediated efflux. Clin Pharmacokinet 46:777-785
77. Iisalo E (1977) Clinical pharmacokinetics of digoxin. Clin Pharmacokinet 2:1-16
78. Ingels F, Beck B, Oth M, Augustijns P (2004) Effect of simulated intestinal fluid on drug permeability estimation across Caco-2 monolayers. Int J Pharm 274:221-232
79. Ito S, Koren G, Harper PA, Silverman M (1993) Energy-dependent transport of digoxin across renal tubular cell monolayers (LLC-PK1). Can J Physiol Pharmacol 71:40-47
80. Ito S, Woodland C, Harper PA, Koren G (1993) P-glycoprotein-mediated renal tubular secretion of digoxin: the toxicological significance of the urine-blood barrier model. Life Sci 53: L25-L31
81. Jalava KM, Partanen J, Neuvonen PJ (1997) Itraconazole decreases renal clearance of digoxin. Ther Drug Monit 19:609-613
82. Johne A, Brockmoller J, Bauer S, Maurer A, Langheinrich M, Roots I (1999) Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum). Clin Pharmacol Ther 66:338-345
83. Johne A, Kopke K, Gerloff T, Mai I, Rietbrock S, Meisel C, Hoffmeyer S, Kerb R, Fromm MF, Brinkmann U, Eichelbaum M, Brockmoller J, Cascorbi I, Roots I (2002) Modulation of steady-state kinetics of digoxin by haplotypes of the P-glycoprotein MDR1 gene. Clin Pharmacol Ther 72:584-594
84. Johnson BM, Zhang P, Schuetz JD, Brouwer KL (2006) Characterization of transport protein expression in multidrug resistance-associated protein (mrp) 2-deficient rats. Drug Metab Dispos 34:556-562
85. Josefsson K, Bergan T, Magni L (1982) Dose-related pharmacokinetics after oral administration of a new formulation of erythromycin base. Br J Clin Pharmacol 13:685-691 (Pubitemid 13139885)
86. Kawahara M, Sakata A, Miyashita T, Tamai I, Tsuji A (1999) Physiologically based pharmacokinetics of digoxin in mdr1a knockout mice. J Pharm Sci 88:1281-1287
87. Keogh JP, Kunta JR (2006) Development, validation and utility of an in vitro technique for assessment of potential clinical drug-drug interactions involving P-glycoprotein. Eur J Pharm Sci 27:543-554
88. Keshavarzian A, Isaac RM (1993) Erythromycin accelerates gastric emptying of indigestible solids and transpyloric migration of the tip of an enteral feeding tube in fasting and fed states. Am J Gastroenterol 88:193-197
89. Kim RB, Wandel C, Leake B, Cvetkovic M, Fromm MF, Dempsey PJ, Roden MM, Belas F, Chaudhary AK, Roden DM, Wood AJ, Wilkinson GR (1999) Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein. Pharm Res 16:408-414
90. Kimchi-Sarfaty C, Oh JM, Kim IW, Sauna ZE, Calcagno AM, Ambudkar SV, Gottesman MM (2007) A "silent" polymorphism in the MDR1 gene changes substrate specificity. Science 315:525-528 (Pubitemid 46175758)
91. Kirby BJ, Kalhorn T, Hebert M, Easterling T, Unadkat JD (2008) Sensitive and specific LC-MS assay for quantification of digoxin in human plasma and urine. Biomed Chromatogr 22:712-718
92. Klaassen CD, Lu H (2008) Xenobiotic transporters: ascribing function from gene knockout and mutation studies. Toxicol Sci 101:186-196
93. Kodawara T, Masuda S, Wakasugi H, Uwai Y, Futami T, Saito H, Abe T, Inu K (2002) Organic anion transporter oatp2-mediated interaction between digoxin and amiodarone in the rat liver. Pharm Res 19:738-743
94. Kovarik JM, Rigaudy L, Guerret M, Gerbeau C, Rost KL (1999) Longitudinal assessment of a P-glycoprotein-mediated drug interaction of valspodar on digoxin. Clin Pharmacol Ther 66:391-400
95. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B (2001) Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology 120:525-533
96. Kurata Y, Ieiri I, Kimura M, Morita T, Irie S, Urae A, Ohdo S, Ohtani H, Sawada Y, Higuchi S, Otsubo K (2002) Role of human MDR1 gene polymorphism in bioavailability and interaction of digoxin, a substrate of P-glycoprotein. Clin Pharmacol Ther 72:209-219
97. Kurzawski M, Bartnicka L, Florczak M, Gornik W, Drozdzik M (2007) Impact of ABCB1 (MDR1) gene polymorphism and P-glycoprotein inhibitors on digoxin serum concentration in congestive heart failure patients. Pharmacol Rep 59:107-111 (Pubitemid 46522710)
98. Lacarelle B, Rahmani R, De Sousa G, Durand A, Placidi M, Cano JP (1991) Metabolism of digoxin, digoxigenin digitoxosides and digoxigenin in human hepatocytes and liver microsomes. Fundam Clin Pharmacol 5:567-582
99. Lam JL, Shugarts SB, Okochi H, Benet LZ (2006) Elucidating the effect of final-day dosing of rifampin in induction studies on hepatic drug disposition and metabolism. J Pharmacol Exp Ther 319:864-870
100. Larsen UL, Hyldahl OL, Guldborg NC, Eriksen J, Jakobsen P, Ostergaard M, Autrup H, Andersen V (2007) Human intestinal P-glycoprotein activity estimated by the model substrate digoxin. Scand J Clin Lab Invest 67:123-134
101. Lau YY, Wu CY, Okochi H, Benet LZ (2004) Ex situ inhibition of hepatic uptake and efflux significantly changes metabolism: hepatic enzyme-transporter interplay. J Pharmacol Exp Ther 308:1040-1045
102. Le Petit G (1985) The pH-dependent lipid solubility of drug groups. Pharmazie 40:797-798
103. Lemahieu WP, Maes BD, Verbeke K, Vanrenterghem Y (2004) CYP3A4 and P-glycoprotein activity in healthy controls and transplant patients on cyclosporin vs. tacrolimus vs. sirolimus. Am J Transplant 4:1514-1522
104. Lindenbaum J, Rund DG, Butler VP Jr, Tse-Eng D, Saha JR (1981) Inactivation of digoxin by the gut flora: reversal by antibiotic therapy. N Engl J Med 305:789-794
105. Lindenberg M, Kopp S, Dressman JB (2004) Classification of orally administered drugs on the World Health Organization Model list of Essential Medicines according to the biopharmaceutics classification system. Eur J Pharm Biopharm 58:265-278
106. Lown KS, Mayo RR, Leichtman AB, Hsiao HL, Turgeon DK, Schmiedlin-Ren P, Brown MB, Guo W, Rossi SJ, Benet LZ, Watkins PB (1997) Role of intestinal P-glycoprotein (mdr1) in interpatient variation in the oral bioavailability of cyclosporine. Clin Pharmacol Ther 62:248-260
107. Luo G, Cunningham M, Kim S, Burn T, Lin J, Sinz M, Hamilton G, Rizzo C, Jolley S, Gilbert D, Downey A, Mudra D, Graham R, Carroll K, Xie J, Madan A, Parkinson A, Christ D, Selling B, LeCluyse E, Gan LS (2002) CYP3A4 induction by drugs: correlation between a pregnane X receptor reporter gene assay and CYP3A4 expression in human hepatocytes. Drug Metab Dispos 30:795-804
108. Manninen V, Apajalahti A, Melin J, Karesoja M (1973) Altered absorption of digoxin in patients given propantheline and metoclopramide. Lancet 1:398-400
109. Manninen V, Apajalahti A, Simonen H, Reissell P (1973) Effect of propantheline and metoclopramide on absorption of digoxin. Lancet 1:1118-1119
110. Marzolini C, Paus E, Buclin T, Kim RB (2004) Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther 75:13-33
111. Mayer U, Wagenaar E, Beijnen JH, Smit JW, Meijer DK, van Asperen J, Borst P, Schinkel AH (1996) Substantial excretion of digoxin via the intestinal mucosa and prevention of long-term digoxin accumulation in the brain by the mdr 1a P-glycoprotein. Br J Pharmacol 119:1038-1044
112. Mayer U, Wagenaar E, Dorobek B, Beijnen JH, Borst P, Schinkel AH (1997) Full blockade of intestinal P-glycoprotein and extensive inhibition of blood-brain barrier P-glycoprotein by oral treatment of mice with PSC833. J Clin Invest 100:2430-2436
113. Meier Y, Eloranta JJ, Darimont J, Ismair MG, Hiller C, Fried M, Kullak-Ublick GA, Vavricka SR (2007) Regional distribution of solute carrier mRNA expression along the human intestinal tract. Drug Metab Dispos 35:590-594
114. Mikkaichi T, Suzuki T, Onogawa T, Tanemoto M, Mizutamari H, Okada M, Chaki T, Masuda S, Tokui T, Eto N, Abe M, Satoh F, Unno M, Hishinuma T, Inui K, Ito S, Goto J, Abe T (2004) Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney. Proc Natl Acad Sci USA 101:3569-3574
115. Mols R, Brouwers J, Schinkel AH, Annaert P, Augustijns P (2009) Intestinal perfusion with mesenteric blood sampling in wild-type and knockout mice: evaluation of a novel tool in biopharmaceutical drug profiling. Drug Metab Dispos 37:1334-1337
116. Moore LB, Goodwin B, Jones SA, Wisely GB, Serabjit-Singh CJ, Willson TM, Collins JL, Kliewer SA (2000) St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Acad Sci USA 97:7500-7502
117. Morita Y, Sakaeda T, Horinouchi M, Nakamura T, Kuroda K, Miki I, Yoshimura K, Sakai T, Shirasaka D, Tamura T, Aoyama N, Kasuga M, Okumura K (2003) MDR1 genotype-related duodenal absorption rate of digoxin in healthy Japanese subjects. Pharm Res 20:552-556
118. Moriya Y, Nakamura T, Horinouchi M, Sakaeda T, Tamura T, Aoyama N, Shirakawa T, Gotoh A, Fujimoto S, Matsuo M, Kasuga M, Okumura K (2002) Effects of polymorphisms of MDR1, MRP1, and MRP2 genes on their mRNA expression levels in duodenal enterocytes of healthy Japanese subjects. Biol Pharm Bull 25:1356-1359
119. Mouly S, Paine MF (2003) P-glycoprotein increases from proximal to distal regions of human small intestine. Pharm Res 20:1595-1599
120. Mueller SC, Uehleke B, Woehling H, Petzsch M, Majcher-Peszynska J, Hehl EM, Sievers H, Frank B, Riethling AK, Drewelow B (2004) Effect of St John's wort dose and preparations on the pharmacokinetics of digoxin. Clin Pharmacol Ther 75:546-557
121. Mujais SK, Fouad FM, Textor SC, Tarazi RC, Bravo EL, Hart N, Gifford RW Jr (1984) Transient renal dysfunction during initial inhibition of converting enzyme in congestive heart failure. Br Heart J 52:63-71
122. Murakami T, Takano M (2008) Intestinal efflux transporters and drug absorption. Expert Opin Drug Metab Toxicol 4:923-939
123. Nademanee K, Kannan R, Hendrickson J, Ookhtens M, Kay I, Singh BN (1984) Amiodarone-digoxin interaction: clinical significance, time course of development, potential pharmacokinetic mechanisms and therapeutic implications. J Am Coll Cardiol 4:111-116
124. Nakamura T, Sakaeda T, Horinouchi M, Tamura T, Aoyama N, Shirakawa T, Matsuo M, Kasuga M, Okumura K (2002) Effect of the mutation (C3435T) at exon 26 of the MDR1 gene on expression level of MDR1 messenger ribonucleic acid in duodenal enterocytes of healthy Japanese subjects. Clin Pharmacol Ther 71:297-303
125. Naslund E, Bogefors J, Gryback P, Jacobsson H, Hellstrom PM (2000) Gastric emptying: comparison of scintigraphic, polyethylene glycol dilution, and paracetamol tracer assessment techniques. Scand J Gastroenterol 35:375-379
126. Neuhoff S, Langguth P, Dressler C, Andersson TB, Regardh CG, Spahn-Langguth H (2000) Affinities at the verapamil binding site of MDR1-encoded P-glycoprotein: drugs and analogs, stereoisomers and metabolites. Int J Clin Pharmacol Ther 38:168-179
127. Neuhoff S, Ungell AL, Zamora I, Artursson P (2003) pH-dependent bidirectional transport of weakly basic drugs across Caco-2 monolayers: implications for drug-drug interactions. Pharm Res 20:1141-1148
128. Ni J, Ouyang H, Aiello M, Seto C, Borbridge L, Sakuma T, Ellis R, Welty D, Acheampong A (2008) Microdosing assessment to evaluate pharmacokinetics and drug metabolism in rats using liquid chromatography-tandem mass spectrometry. Pharm Res 25:1572-1582
129. Noe B, Hagenbuch B, Stieger B, Meier PJ (1997) Isolation of a multispecific organic anion and cardiac glycoside transporter from rat brain. Proc Natl Acad Sci USA 94:10346-10350
130. Noviello E, Allievi E, Russo P, Parodi S (1997) Effects of Dex-Verapamil on Doxorubicin cytotoxicity in P388 murine leukemia cells. Anticancer Drug Des 12:261-276
131. Oertel R, Richter K, Trausch B, Berndt A, Gramatte T, Kirch W (1994) Elucidation of the structure of talinolol metabolites in man. Determination of talinolol and hydroxylated talinolol metabolites in urine and analysis of talinolol in serum. J Chromatogr B Biomed Appl 660:353-363
132. Ofer M, Wolffram S, Koggel A, Spahn-Langguth H, Langguth P (2005) Modulation of drug transport by selected flavonoids: involvement of P-gp and OCT? Eur J Pharm Sci 25:263-271
133. Okamura N, Hirai M, Tanigawara Y, Tanaka K, Yasuhara M, Ueda K, Komano T, Hori R (1993) Digoxin-cyclosporin A interaction: modulation of the multidrug transporter P-glycoprotein in the kidney. J Pharmacol Exp Ther 266:1614-1619
134. Oswald S, Haenisch S, Fricke C, Sudhop T, Remmler C, Giessmann T, Jedlitschky G, Adam U, Dazert E, Warzok R, Wacke W, Cascorbi I, Kroemer HK, Weitschies W, von Bergmann K, Siegmund W (2006) Intestinal expression of P-glycoprotein (ABCB1), multidrug resistance associated protein 2 (ABCC2), and uridine diphosphate-glucuronosyltransferase 1A1 predicts the disposition and modulates the effects of the cholesterol absorption inhibitor ezetimibe in humans. Clin Pharmacol Ther 79:206-217
135. Oswald S, Westrup S, Grube M, Kroemer HK, Weitschies W, Siegmund W (2006b). Disposition and sterol-lowering effect of ezetimibe in multidrug resistance-associated protein 2-deficient rats. Journal of Pharmacolology and Experimental Therapeutics 318:1293-9.
136. Pauli-Magnus C, Murdter T, Godel A, Mettang T, Eichelbaum M, Klotz U, Fromm MF (2001) P-glycoprotein-mediated transport of digitoxin, alpha-methyldigoxin and beta-acetyldigoxin. Naunyn Schmiedebergs Arch Pharmacol 363:337-343
137. Pedersen KE, Christiansen BD, Klitgaard NA, Nielsen-Kudsk F (1983) Effect of quinidine on digoxin bioavailability. Eur J Clin Pharmacol 24:41-47
138. Piergies AA, Worwag EM, Atkinson AJ Jr (1994) A concurrent audit of high digoxin plasma levels. Clin Pharmacol Ther 55:353-358
139. Rautio J, Humphreys JE, Webster LO, Balakrishnan A, Keogh JP, Kunta JR, Serabjit-Singh CJ, Polli JW (2006) In vitro p-glycoprotein inhibition assays for assessment of clinical drug interaction potential of new drug candidates: a recommendation for probe substrates. Drug Metab Dispos 34:786-792
140. Rengelshausen J, Goggelmann C, Burhenne J, Riedel KD, Ludwig J, Weiss J, Mikus G, Walter-Sack I, Haefeli WE (2003) Contribution of increased oral bioavailability and reduced nonglomerular renal clearance of digoxin to the digoxin-clarithromycin interaction. Br J Clin Pharmacol 56:32-38
141. Rodin SM, Johnson BF, Wilson J, Ritchie P, Johnson J (1988) Comparative effects of verapamil and isradipine on steady-state digoxin kinetics. Clin Pharmacol Ther 43:668-672
142. Rowland M, Benet LZ, Graham GG (1973) Clearance concepts in pharmacokinetics. J Pharmacokinet Biopharm 1:123-136
143. Sakaeda T, Nakamura T, Horinouchi M, Kakumoto M, Ohmoto N, Sakai T, Morita Y, Tamura T, Aoyama N, Hirai M, Kasuga M, Okumura K (2001) MDR1 genotype-related pharmacokinetics of digoxin after single oral administration in healthy Japanese subjects. Pharm Res 18:1400-1404
144. Schaefer M, Roots I, Gerloff T (2006) In-vitro transport characteristics discriminate wild-type ABCB1 (MDR1) from ALA893SER and ALA893THR polymorphisms. Pharmacogenet Genomics 16:855-861
145. Schinkel AH, Wagenaar E, van Deemter L, Mol CA, Borst P (1995) Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A. J Clin Invest 96:1698-1705
146. Schinkel AH, Mayer U, Wagenaar E, Mol CA, van Deemter L, Smit JJ, van der Valk MA, Voordouw AC, Spits H, van Tellingen O, Zijlmans JM, Fibbe WE, Borst P (1997) Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins. Proc Natl Acad Sci USA 94:4028-4033
147. Schmoldt A, Ahsendorf B (1980) Cleavage of digoxigenin digitoxosides by rat liver microsomes. Eur J Drug Metab Pharmacokinet 5:225-232
148. Schuetz EG, Beck WT, Schuetz JD (1996) Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately up-regulate these proteins in human colon carcinoma cells. Mol Pharmacol 49:311-318
149. Schupke H, Hempel R, Eckardt R, Kronbach T (1996) Identification of talinolol metabolites in urine of man, dog, rat and mouse after oral administration by high-performance liquid chromatography-thermospray tandem mass spectrometry. J Mass Spectrom 31:1371-1381
150. Schwartz JB (2003) The influence of sex on pharmacokinetics. Clin Pharmacokinet 42:107-121
151. Schwarz UI, Gramatte T, Krappweis J, Berndt A, Oertel R, von Richter O, Kirch W (1999) Unexpected effect of verapamil on oral bioavailability of the beta-blocker talinolol in humans. Clin Pharmacol Ther 65:283-290
152. Schwarz UI, Gramatte T, Krappweis J, Oertel R, Kirch W (2000) P-glycoprotein inhibitor erythromycin increases oral bioavailability of talinolol in humans. Int J Clin Pharmacol Ther 38:161-167
153. Schwarz UI, Dresser GK, Oertel R K R B (2001) Talinolol-verapamil interaction is not solely due to p-glycoprotein inhibition. Clin Pharmacol Ther 69: PIII-86
154. Schwarz UI, Hanso H, Oertel R, Miehlke S, Kuhlisch E, Glaeser H, Hitzl M, Dresser GK, Kim RB, Kirch W (2007) Induction of intestinal P-glycoprotein by St John's wort reduces the oral bioavailability of talinolol. Clin Pharmacol Ther 81:669-678
155. Seithel A, Karlsson J, Hilgendorf C, Bjorquist A, Ungell AL (2006) 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 28:291-299
156. Severijnen R, Bayat N, Bakker H, Tolboom J, Bongaerts G (2004) Enteral drug absorption in patients with short small bowel: a review. Clin Pharmacokinet 43:951-962
157. Shirasaka Y, Kawasaki M, Sakane T, Omatsu H, Moriya Y, Nakamura T, Sakaeda T, Okumura K, Langguth P, Yamashita S (2006) Induction of human P-glycoprotein in Caco-2 cells: development of a highly sensitive assay system for P-glycoprotein-mediated drug transport. Drug Metab Pharmacokinet 21:414-423
158. Shirasaka Y, Li Y, Shibue Y, Kuraoka E, Spahn-Langguth H, Kato Y, Langguth P, Tamai I (2009) Concentration-dependent effect of naringin on intestinal absorption of beta (1)-adrenoceptor antagonist talinolol mediated by p-glycoprotein and organic anion transporting polypeptide (Oatp). Pharm Res 26:560-567
159. Shirasaka Y, Kuraoka E, Spahn-Langguth H, Nakanishi T, Langguth P, Tamai I (2010) Species difference in the effect of grapefruit juice on intestinal absorption of talinolol between human and rat. J Pharmacol Exp Ther 332:181-189
160. Shitara Y, Sugiyama D, Kusuhara H, Kato Y, Abe T, Meier PJ, Itoh T, Sugiyama Y (2002) Comparative inhibitory effects of different compounds on rat oatpl (slc21a1) - and Oatp2 (Slc21a5)-mediated transport. Pharm Res 19:147-153
161. Shugarts S, Benet LZ (2009) The role of transporters in the pharmacokinetics of orally administered drugs. Pharm Res 26:2039-2054
162. Siegmund W, Altmannsberger S, Paneitz A, Hecker U, Zschiesche M, Franke G, Meng W, Warzok R, Schroeder E, Sperker B, Terhaag B, Cascorbi I, Kroemer HK (2002) Effect of levothyroxine administration on intestinal P-glycoprotein expression: consequences for drug disposition. Clin Pharmacol Ther 72:256-264
163. Siegmund W, Ludwig K, Giessmann T, Dazert P, Schroeder E, Sperker B, Warzok R, Kroemer HK, Cascorbi I (2002) The effects of the human MDR1 genotype on the expression of duodenal P-glycoprotein and disposition of the probe drug talinolol. Clin Pharmacol Ther 72:572-583
164. Siegmund W, Ludwig K, Engel G, Zschiesche M, Franke G, Hoffmann A, Terhaag B, Weitschies W (2003) Variability of intestinal expression of P-glycoprotein in healthy volunteers as described by absorption of talinolol from four bioequivalent tablets. J Pharm Sci 92:604-610
165. Simon GL, Gorbach SL (1984) Intestinal flora in health and disease. Gastroenterology 86:174-193
166. Song S, Suzuki H, Kawai R, Sugiyama Y (1999) Effect of PSC 833, a P-glycoprotein modulator, on the disposition of vincristine and digoxin in rats. Drug Metab Dispos 27:689-694
167. Spahn-Langguth H, Langguth P (2001) Grapefruit juice enhances intestinal absorption of the P-glycoprotein substrate talinolol. Eur J Pharm Sci 12:361-367
168. 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
169. Steiness E (1974) Renal tubular secretion of digoxin. Circulation 50:103-107
170. Steinijans VW, Sauter R, Hauschke D, Diletti E, Schall R, Luus HG, Elze M, Blume H, Hoffmann C, Franke G (1995) Reference tables for the intrasubject coefficient of variation in bioequivalence studies. Int J Clin Pharmacol Ther 33:427-430
171. Sugawara I, Kataoka I, Morishita Y, Hamada H, Tsuruo T, Itoyama S, Mori S (1988) Tissue distribution of P-glycoprotein encoded by a multidrug-resistant gene as revealed by a monoclonal antibody, MRK 16. Cancer Res 48:1926-1929
172. Sumner DJ, Russell AJ (1976) Digoxin pharmacokinetics: multicompartmental analysis and its clinical implications. Br J Clin Pharmacol 3:221-229
173. Takano M, Yumoto R, Murakami T (2006) Expression and function of efflux drug transporters in the intestine. Pharmacol Ther 109:137-161
174. Takara K, Kakumoto M, Tanigawara Y, Funakoshi J, Sakaeda T, Okumura K (2002) Interaction of digoxin with antihypertensive drugs via MDR1. Life Sci 70:1491-1500
175. Takara K, Tsujimoto M, Ohnishi N, Yokoyama T (2002) Digoxin up-regulates MDR1 in human colon carcinoma Caco-2 cells. Biochem Biophys Res Commun 292:190-194
176. Tanigawara Y, Okamura N, Hirai M, Yasuhara M, Ueda K, Kioka N, Komano T, Hori R (1992) Transport of digoxin by human P-glycoprotein expressed in a porcine kidney epithelial cell line (LLC-PK1). J Pharmacol Exp Ther 263:840-845
177. Taub ME, Podila L, Ely D, Almeida I (2005) Functional assessment of multiple P-glycoprotein (P-gp) probe substrates: influence of cell line and modulator concentration on P-gp activity. Drug Metab Dispos 33:1679-1687
178. Tenero D, Boike S, Boyle D, Ilson B, Fesniak HF, Brozena S, Jorkasky D (2000) Steady-state pharmacokinetics of carvedilol and its enantiomers in patients with congestive heart failure. J Clin Pharmacol 40:844-853
179. Terhaag B, Gramatte T, Richter K, Voss J, Feller K (1989) The biliary elimination of the selective beta-receptor blocking drug talinolol in man. Int J Clin Pharmacol Ther Toxicol 27:170-172
180. Thiebaut F, Tsuruo T, Hamada H, Gottesman MM, Pastan I, Willingham MC (1987) Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci USA 84:7735-7738
181. Thorn M, Finnstrom N, Lundgren S, Rane A, Loof L (2005) Cytochromes P450 and MDR1 mRNA expression along the human gastrointestinal tract. Br J Clin Pharmacol 60:54-60
182. Tran CD, Timmins P, Conway BR, Irwin WJ (2002) Investigation of the coordinated functional activities of cytochrome P450 3A4 and P-glycoprotein in limiting the absorption of xenobiotics in Caco-2 cells. J Pharm Sci 91:117-128
183. Trausch B, Oertel R, Richter K, Gramatte T (1995) Disposition and bioavailability of the beta 1-adrenoceptor antagonist talinolol in man. Biopharm Drug Dispos 16:403-414
184. Triscari J, Swanson BN, Willard DA, Cohen AI, Devault A, Pan HY (1993) Steady state serum concentrations of pravastatin and digoxin when given in combination. Br J Clin Pharmacol 36:263-265
185. Troutman MD, Thakker DR (2003) Efflux ratio cannot assess P-glycoprotein-mediated attenuation of absorptive transport: asymmetric effect of P-glycoprotein on absorptive and secretory transport across Caco-2 cell monolayers. Pharm Res 20:1200-1209
186. Tsujimoto M, Dan Y, Hirata S, Ohtani H, Sawada Y (2008) Influence of SLCO1B3 gene polymorphism on the pharmacokinetics of digoxin in terminal renal failure. Drug Metab Pharmacokinet 23:406-411
187. Tubic M, Wagner D, Spahn-Langguth H, Bolger MB, Langguth P (2006) In silico modeling of non-linear drug absorption for the P-gp substrate talinolol and of consequences for the resulting pharmacodynamic effect. Pharm Res 23:1712-1720
188. Tuncok Y, Hazan E, Oto O, Guven H, Catalyurek H, Kalkan S (1997) Relationship between high serum digoxin levels and toxicity. Int J Clin Pharmacol Ther 35:366-368
189. Urquhart BL, Tirona RG, Kim RB (2007) Nuclear receptors and the regulation of drug-metabolizing enzymes and drug transporters: implications for interindividual variability in response to drugs. J Clin Pharmacol 47:566-578
190. Verstuyft C, Schwab M, Schaeffeler E, Kerb R, Brinkmann U, Jaillon P, Funck-Brentano C, Becquemont L (2003) Digoxin pharmacokinetics and MDR1 genetic polymorphisms. Eur J Clin Pharmacol 58:809-812 (Pubitemid 36577811)
191. Viswanathan CT, Bansal S, Booth B, DeStefano AJ, Rose MJ, Sailstad J, Shah VP, Skelly JP, Swann PG, Weiner R (2007) Quantitative bioanalytical methods validation and implementation: best practices for chromatographic and ligand binding assays. Pharm Res 24:1962-73. (Pubitemid 47389236)
192. Wacher VJ, Wu CY, Benet LZ (1995) Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P-glycoprotein: implications for drug delivery and activity in cancer chemotherapy. Mol Carcinog 13:129-134
193. Wakasugi H, Yano I, Ito T, Hashida T, Futami T, Nohara R, Sasayama S, Inui K (1998) Effect of clarithromycin on renal excretion of digoxin: interaction with P-glycoprotein. Clin Pharmacol Ther 64:123-128
194. Wan CK, Zhu GY, Shen XL, Chattopadhyay A, Dey S, Fong WF (2006) Gomisin A alters substrate interaction and reverses P-glycoprotein-mediated multidrug resistance in HepG2-DR cells. Biochem Pharmacol 72:824-837
195. Wandel C, Kim RB, Kajiji S, Guengerich P, Wilkinson GR, Wood AJ (1999) P-glycoprotein and cytochrome P-450 3A inhibition: dissociation of inhibitory potencies. Cancer Res 59:3944-3948
196. Wang Y, Cao J, Zeng S (2005) Involvement of P-glycoprotein in regulating cellular levels of Ginkgo flavonols: quercetin, kaempferol, and isorhamnetin. J Pharm Pharmacol 57:751-758
197. Watson E, Clark DR, Kalman SM (1973) Identification by gas chromatography-mass spectroscopy of dihydrodigoxin - a metabolite of digoxin in man. J Pharmacol Exp Ther 184:424-431
198. Weale AR, Edwards AG, Bailey M, Lear PA (2005) Intestinal adaptation after massive intestinal resection. Postgrad Med J 81:178-184
199. Weiss M, Hung DY, Poenicke K, Roberts MS (2008) Kinetic analysis of saturable hepatic uptake of digoxin and its inhibition by rifampicin. Eur J Pharm Sci 34:345-350
200. Weitschies W, Bernsdorf A, Giessmann T, Zschiesche M, Modess C, Hartmann V, Mrazek C, Wegner D, Nagel S, Siegmund W (2005) The talinolol double-peak phenomenon is likely caused by presystemic processing after uptake from gut lumen. Pharm Res 22:728-735
201. Wentworth JM, Agostini M, Love J, Schwabe JW, Chatterjee VK (2000) St John's wort, a herbal antidepressant, activates the steroid X receptor. J Endocrinol 166: R11-R16
202. Westphal K, Weinbrenner A, Giessmann T, Stuhr M, Franke G, Zschiesche M, Oertel R, Terhaag B, Kroemer HK, Siegmund W (2000) Oral bioavailability of digoxin is enhanced by talinolol: evidence for involvement of intestinal P-glycoprotein. Clin Pharmacol Ther 68:6-12
203. Westphal K, Weinbrenner A, Zschiesche M, Franke G, Knoke M, Oertel R, Fritz P, von Richter O, Warzok R, Hachenberg T, Kauffmann 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. Clin Pharmacol Ther 68:345-355
204. Wetterich U, Spahn-Langguth H, Mutschler E, Terhaag B, Rosch W, Langguth P (1996) Evidence for intestinal secretion as an additional clearance pathway of talinolol enantiomers: concentration-and dose-dependent absorption in vitro and in vivo. Pharm Res 13:514-522
205. Wilding IR, Hardy JG, Sparrow RA, Davis SS, Daly PB, English JR (1992) In vivo evaluation of enteric-coated naproxen tablets using gamma scintigraphy. Pharm Res 9:1436-1441
206. Wu CY, Benet LZ (2005) Predicting drug disposition via application of BCS: transport/absorption/elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm Res 22:11-23
207. Xu P, Jiang ZP, Zhang BK, Tu JY, Li HD (2008) Impact of MDR1 haplotypes derived from C1236T, G2677T/A and C3435T on the pharmacokinetics of single-dose oral digoxin in healthy Chinese volunteers. Pharmacology 82:221-227
208. Zhang S, Morris ME (2003) Effect of the flavonoids biochanin A and silymarin on the P-glycoprotein-mediated transport of digoxin and vinblastine in human intestinal Caco-2 cells. Pharm Res 20:1184-1191
209. Zhang S, Morris ME (2003) Effects of the flavonoids biochanin A, morin, phloretin, and silymarin on P-glycoprotein-mediated transport. J Pharmacol Exp Ther 304:1258-1267
210. Zhang L, Schaner ME, Giacomini KM (1998) Functional characterization of an organic cation transporter (hOCT1) in a transiently transfected human cell line (HeLa). J Pharmacol Exp Ther 286:354-361 (Pubitemid 28318011)
211. Zimmermann C, Gutmann H, Hruz P, Gutzwiller JP, Beglinger C, Drewe J (2005) Mapping of multidrug resistance gene 1 and multidrug resistance- associated protein isoform 1 to 5 mRNA expression along the human intestinal tract. Drug Metab Dispos 33:219-224
212. Zschiesche M, Lemma GL, Klebingat KJ, Franke G, Terhaag B, Hoffmann A, Gramatte T, Kroemer HK, Siegmund W (2002) Stereoselective disposition of talinolol in man. J Pharm Sci 91:303-311