In situ perfusion in rodents to explore intestinal drug absorption: Challenges and opportunities

International Journal of Pharmaceutics

Volumn 478, Issue 2, 2015, Pages 665-681

  Stappaerts, Jef ^a   Brouwers, Joachim ^a   Annaert, Pieter ^a   Augustijns, Patrick ^a  

^a DEPARTMENT OF PHARMACEUTICAL AND PHARMACOLOGICAL SCIENCES   (Belgium)

Author keywords

Intestinal perfusion; Knockout animals; Site dependent absorption; Solubility permeability interplay; Supersaturation; Transporter metabolism interplay

Indexed keywords

AGE; ARTICLE; BLOOD SAMPLING; BLOOD VESSEL PERMEABILITY; CACO 2 CELL LINE; DRUG ABSORPTION; DRUG EXCRETION; DRUG METABOLISM; DRUG PENETRATION; DRUG SOLUBILITY; DRUG TRANSPORT; IN SITU INTESTINAL PERFUSION; INTESTINE ABSORPTION; INTESTINE LOOP; INTESTINE MUCOSA PERMEABILITY; INTESTINE PERFUSION; INTRAVENOUS DRUG ADMINISTRATION; MESENTERIC VEIN; MOUSE; NONHUMAN; PERMEABILITY BARRIER; PROTEIN EXPRESSION; RAT; SMALL INTESTINE; TRANSGENIC ANIMAL; ANIMAL; HUMAN; METABOLISM; PERFUSION; PERMEABILITY;

DRUG;

ANIMALS; HUMANS; INTESTINAL ABSORPTION; INTESTINE, SMALL; PERFUSION; PERMEABILITY; PHARMACEUTICAL PREPARATIONS;

EID: 84918770864     PISSN: 03785173     EISSN: 18733476     Source Type: Journal    
DOI: 10.1016/j.ijpharm.2014.11.035     Document Type: Review

References (145)

1. B.S. Abuasal, M.B. Bolger, D.K. Walker, and A. Kaddoumi In silico modeling for the nonlinear absorption kinetics of UK-343,664: a P-gp and CYP3A4 substrate Mol. Pharm. 9 2012 492 504 10.1021/mp200275j
2. Y. Adachi, H. Suzuki, A.H. Schinkel, and Y. Sugiyama Role of breast cancer resistance protein (Bcrp1/Abcg2) in the extrusion of glucuronide and sulfate conjugates from enterocytes to intestinal lumen Mol. Pharmacol. 67 2005 923 928 10.1124/mol.104.007393
3. M.U. Anby, H.D. Williams, M. McIntosh, H. Benameur, G.A. Edwards, C.W. Pouton, and C.J.H. Porter Lipid digestion as a trigger for supersaturation: evaluation of the impact of supersaturation stabilization on the in vitro and in vivo performance of self-emulsifying drug delivery systems Mol. Pharm. 9 2012 2063 2079 10.1021/mp300164u
4. P. Annaert, J.J. Tukker, J. van Gelder, L. Naesens, E. de Clercq, G. van Den Mooter, R. Kinget, and P. Augustijns In vitro, ex vivo, and in situ intestinal absorption characteristics of the antiviral ester prodrug adefovir dipivoxil J. Pharm. Sci. 89 2000 1054 1062
5. H. Arakawa, Y. Shirasaka, M. Haga, T. Nakanishi, and I. Tamai Active intestinal absorption of fluoroquinolone antibacterial agent ciprofloxacin by organic anion transporting polypeptide, Oatp1a5 Biopharm. Drug Dispos. 33 2012 332 341 10.1002/bdd.1809
6. K. Arimori, S. Miyamoto, K. Fukuda, C. Nakamura, and M. Nakano Characteristic difference in gastrointestinal excretion of clarithromycin and roxithromycin Biopharm. Drug Dispos. 19 1998 433 438
7. Artursson, P., Palm, K., Luthman, K., 2001. Caco-2 monolayers in experimental and theoretical predictions of drug transport, 27-43.
8. P. Augustijns, B. Wuyts, B. Hens, P. Annaert, J. Butler, and J. Brouwers A review of drug solubility in human intestinal fluids: implications for the prediction of oral absorption Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci. 57 2014 322 332 10.1016/j.ejps.2013.08.027
9. K. Beaumont, R. Webster, I. Gardner, and K. Dack Design of ester prodrugs to enhance oral absorption of poorly permeable compounds: challenges to the discovery scientist Curr. Drug Metab. 4 2003 461 485
10. A. Beig, R. Agbaria, and A. Dahan Oral delivery of lipophilic drugs: the tradeoff between solubility increase and permeability decrease when using cyclodextrin-based formulations PLoS One 8 2013 e68237 10.1371/journal.pone.0068237
11. L.Z. Benet, C.L. Cummins, and C.Y. Wu Unmasking the dynamic interplay between efflux transporters and metabolic enzymes Int. J. Pharm. 277 2004 3 9 10.1016/j.ijpharm.2002.12.002
12. Berggren, S., Gall, C., Wollnitz, N., Ekelund, M., Karlbom, U., Hoogstraate, J., Schrenk, D., Lennernäs, H., 2007. Gene and protein expression of P-glycoprotein, MRP1, MRP2, and CYP3A4 in the small and large human intestine, 252-257.
13. J. Bevernage, J. Brouwers, P. Annaert, and P. Augustijns Drug precipitation-permeation interplay: supersaturation in an absorptive environment Eur. J. Pharm. Biopharm. Off. J. 82 2012 424 428 10.1016/j.ejpb.2012.07.009 Arbeitsgemeinschaft Für Pharm. Verfahrenstechnik EV
14. J. Bevernage, J. Brouwers, M.E. Brewster, and P. Augustijns 2013: Evaluation of gastrointestinal drug supersaturation and precipitation: strategies and issues Int. J. Pharm. 453 2013 25 35 10.1016/j.ijpharm.2012.11.026
15. H. Bohets, P. Annaert, G. Mannens, L. Van Beijsterveldt, K. Anciaux, P. Verboven, W. Meuldermans, and K. Lavrijsen Strategies for absorption screening in drug discovery and development Curr. Top. Med. Chem. 1 2001 367 383
16. A.S. Borde, E.M. Karlsson, K. Andersson, K. Björhall, H. Lennernäs, and B. Abrahamsson Assessment of enzymatic prodrug stability in human, dog and simulated intestinal fluids Eur. J. Pharm. Biopharm. Off. J. 80 2012 630 637 10.1016/j.ejpb.2011.11.011 Arbeitsgemeinschaft Für Pharm. Verfahrenstechnik EV
17. J. Brouwers, and P. Augustijns Resolving intraluminal drug and formulation behavior: Gastrointestinal concentration profiling in humans Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci. 61 2014 2 10 10.1016/j.ejps.2014.01.010
18. Brouwers, J., Tack, J., Augustijns, P., 2007. In vitro behavior of a phosphate ester prodrug of amprenavir in human intestinal fluids and in the Caco-2 system: illustration of intraluminal supersaturation, 302-309.
19. S.T. Buckley, K.J. Frank, G. Fricker, and M. Brandl Biopharmaceutical classification of poorly soluble drugs with respect to enabling formulations Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci. 50 2013 8 16 10.1016/j.ejps.2013.04.002
20. Canaparo, R., Finnström, N., Serpe, L., Nordmark, A., Muntoni, E., Eandi, M., Rane, A., Zara, G.P., 2007. Expression of CYP3A isoforms and P-glycoprotein in human stomach, jejunum and ileum, 1138-1144.
21. X. Cao, S.T. Gibbs, L. Fang, H.A. Miller, C.P. Landowski, H.-C. Shin, H. Lennernas, Y. Zhong, G.L. Amidon, L.X. Yu, and D. Sun Why is it challenging to predict intestinal drug absorption and oral bioavailability in human using rat model Pharmaceutical research 23 8 2006 1675 1686
22. F. Cao, J. Jia, Z. Yin, Y. Gao, L. Sha, Y. Lai, Q. Ping, and Y. Zhang Ethylene glycol-linked amino acid diester prodrugs of oleanolic acid for PepT1- mediated transport: synthesis, intestinal permeability and pharmacokinetics Mol. Pharm. 9 2012 2127 2135 10.1021/mp200447r
23. X. Cao, L.X. Yu, C. Barbaciru, C.P. Landowski, H.-C. Shin, S. Gibbs, H.A. Miller, G.L. Amidon, and D. Sun Permeability dominates in vivo intestinal absorption of P-gp substrate with high solubility and high permeability Mol. Pharm. 2 2005 329 340 10.1021/mp0499104
24. G. Cepinskas, R.D. Specian, and P.R. Kvietys Adaptive cytoprotection in the small intestine: role of mucus Am. J. Physiol. 264 1993 G921 927
25. W.L. Chiou, and A. Barve Linear correlation of the fraction of oral dose absorbed of 64 drugs between humans and rats Pharm. Res. 15 1998 1792 1795
26. E.F. Choo, B. Leake, C. Wandel, H. Imamura, A.J. Wood, G.R. Wilkinson, and R.B. Kim Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes Drug Metab. Dispos. Biol. Fate Chem. 28 2000 655 660
27. C.L. Cummins, L. Salphati, M.J. Reid, and L.Z. Benet In vivo modulation of intestinal CYP3A metabolism by P-glycoprotein: studies using the rat single-pass intestinal perfusion model J. Pharmacol. Exp. Ther. 305 1 2003 306 314
28. A. Dahan, and G.L. Amidon Small intestinal efflux mediated by MRP2 and BCRP shifts sulfasalazine intestinal permeability from high to low, enabling its colonic targeting Am. J. Physiol.-Gastrointestinal Liver Physiol. 297 2 2009 G371 G377
29. A. Dahan, H. Sabit, and G.L. Amidon Multiple efflux pumps are involved in the transepithelial transport of colchicine: combined effect of P-glycoprotein and multidrug resistance-associated protein 2 leads to decreased intestinal absorption throughout the entire small intestine Drug Metab. Dispos. Biol. Fate Chem. 37 2009 2028 2036 10.1124/dmd.109.028282
30. A. Dahan, J.M. Miller, J.M. Hilfinger, S. Yamashita, L.X. Yu, H. LennernaÌs, and G.L. Amidon High-permeability criterion for BCS classification: segmental/pH dependent permeability considerations Mol. Pharm. 7 2010 1827 1834 10.1021/mp100175a
31. A. Dahan, A. Beig, V. Ioffe-Dahan, R. Agbaria, and J.M. Miller The twofold advantage of the amorphous form as an oral drug delivery practice for lipophilic compounds: increased apparent solubility and drug flux through the intestinal membrane AAPS J. 15 2013 347 353 10.1208/s12248-012-9445-3
32. S. Dautrey, K. Felice, A. Petiet, B. Lacour, C. Carbon, and R. Farinotti Active intestinal elimination of ciprofloxacin in rats: modulation by different substrates Br. J. Pharmacol. 127 1999 1728 1734 10.1038/sj.bjp.0702703
33. J.T. Doluisio, N.F. Billups, L.W. Dittert, E.T. Sugita, and J.V. Swintosky Drug absorption. I. An in situ rat gut technique yielding realistic absorption rates J. Pharm. Sci. 58 1969 1196 1200
34. G. Englund, F. Rorsman, A. Rönnblom, U. Karlbom, L. Lazorova, J. Gråsjö, A. Kindmark, and P. Artursson 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 3 2006 269 277
35. A.H. Eriksson, M.V.S. Varma, E.J. Perkins, and C.L. Zimmerman The intestinal absorption of a prodrug of the mGlu2/3 receptor agonist LY354740 is mediated by PEPT1: in situ rat intestinal perfusion studies J. Pharm. Sci. 99 2010 1574 1581 10.1002/jps.21917
36. J. Fallingborg Intraluminal pH of the human gastrointestinal tract Dan. Med. Bull. 46 1999 183 196
37. M. Farooq, and M. Hawksworth The arrival of knockout rats J. Mol. Cloning Genet. Recomb. 01 2012 10.4172/2325-9787.1000e101
38. FDA, 2011. Drug Interactions & Labeling - Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. [WWW Document]. URL http://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/ucm093664htm (accessed 09.10.14).
39. S.M. Fischer, M. Brandl, and G. Fricker Effect of the non-ionic surfactant Poloxamer 188 on passive permeability of poorly soluble drugs across Caco-2 cell monolayers Eur. J. Pharm. Biopharm. Off. J. 79 2011 416 422 10.1016/j.ejpb.2011.04.010 Arbeitsgemeinschaft Für Pharm. Verfahrenstechnik EV
40. L. Fossati, R. Dechaume, E. Hardillier, D. Chevillon, C. Prevost, S. Bolze, and N. Maubon Use of simulated intestinal fluid for Caco-2 permeability assay of lipophilic drugs Int. J. Pharm. 360 2008 148 155 10.1016/j.ijpharm.2008.04.034
41. K.J. Frank, K.M. Rosenblatt, U. Westedt, P. Hölig, J. Rosenberg, M. Mägerlein, G. Fricker, and M. Brandl Amorphous solid dispersion enhances permeation of poorly soluble ABT-102: true supersaturation vs. apparent solubility enhancement Int. J. Pharm. 437 2012 288 293 10.1016/j.ijpharm.2012.08.014
42. W. Gao, M. Kageyama, Y. Inoue, J. Tadano, K. Fukumoto, K. Fukushima, D. Yamasaki, A. Nishimura, Y. Yoshikawa, N. Shibata, and K. Takada Effect of indinavir on the intestinal exsorption of amprenavir: saquinavir and nelfinavir after intravenous administration in rats Biol. Pharm. Bull. 26 2003 199 204
43. I. González-Alvarez, C. Fernández-Teruel, V.G. Casabó-Alós, T.M. Garrigues, J.E. Polli, A. Ruiz-García, and M. Bermejo In situ kinetic modelling of intestinal efflux in rats: functional characterization of segmental differences and correlation with in vitro results Biopharm. Drug Dispos. 28 2007 229 239 10.1002/bdd.548
44. G.E. Granero, and G.L. Amidon 2006: Stability of valacyclovir: implications for its oral bioavailability Int. J. Pharm. 317 2006 14 18 10.1016/j.ijpharm.2006.01.050
45. S.V. Gupta, D. Gupta, J. Sun, A. Dahan, Y. Tsume, J. Hilfinger, K.-D. Lee, and G.L. Amidon 2011: Enhancing the intestinal membrane permeability of zanamivir: a carrier mediated prodrug approach Mol. Pharm. 8 2011 2358 2367 10.1021/mp200291x
46. A. Hanafy, P. Langguth, and H. Spahn-Langguth Pretreatment with potent P-glycoprotein ligands may increase intestinal secretion in rats Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci. 12 2001 405 415
47. H. Han, R.L. de Vrueh, J.K. Rhie, K.M. Covitz, P.L. Smith, C.P. Lee, D.M. Oh, W. Sadée, and G.L. Amidon 5′-Amino acid esters of antiviral nucleosides acyclovir, and AZT are absorbed by the intestinal PEPT1 peptide transporter Pharm. Res. 15 1998 1154 1159
48. D. Herrera-Ruiz, Q. Wang, O.S. Gudmundsson, T.J. Cook, R.L. Smith, T.N. Faria, and G.T. Knipp 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. 3 2001 E9
49. N. Holmstock, R. Mols, P. Annaert, and P. Augustijns In situ intestinal perfusion in knockout mice demonstrates inhibition of intestinal P-glycoprotein by ritonavir causing increased darunavir absorption Drug Metabolism and Disposition 38 9 2010 1407 1410
50. N.F. Holmstock, P.P. Annaert, and P. Augustijns Boosting of HIV protease inhibitors by ritonavir in the intestine: the relative role of Cyp and P-gp Inhibition Based on Caco-2 monolayers versus in situ intestinal perfusion in mice Drug Metab. Dispos. 40 8 2012 1473 1477
51. N. Holmstock, T.D. Bruyn, J. Bevernage, P. Annaert, R. Mols, J. Tack, and P. Augustijns Exploring food effects on indinavir absorption with human intestinal fluids in the mouse intestine Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci. 49 2013 27 32 10.1016/j.ejps.2013.01.012
52. N. Holmstock, F.J. Gonzalez, M. Baes, P. Annaert, and P. Augustijns PXR/CYP3A4-humanized mice for studying drug-drug interactions involving intestinal P-glycoprotein Mol. Pharm. 10 2013 1056 1062 10.1021/mp300512r
53. Y. Hu, D.E. Smith, K. Ma, D. Jappar, W. Thomas, and K.M. Hillgren Targeted disruption of peptide transporter Pept1 gene in mice significantly reduces dipeptide absorption in intestine Mol. Pharm. 5 2008 1122 1130
54. T. Imai, and K. Ohura The role of intestinal carboxylesterase in the oral absorption of prodrugs Curr. Drug Metab. 11 2010 793 805
55. F. Ingels, B. Beck, M. Oth, and P. Augustijns Effect of simulated intestinal fluid on drug permeability estimation across Caco-2 monolayers Int. J. Pharm. 274 1 2004 221 232
56. F. Ingels, S. Deferme, E. Destexhe, M. Oth, G. Van den Mooter, and P. Augustijns Simulated intestinal fluid as transport medium in the Caco-2 cell culture model Int. J. Pharm. 232 2002 183 192
57. F.M. Ingels, and P.F. Augustijns Biological, pharmaceutical, and analytical considerations with respect to the transport media used in the absorption screening system, Caco-2 J. Pharm. Sci. 92 2003 1545 1558 10.1002/jps.10408
58. S.A. Ingersoll, S. Ayyadurai, M.A. Charania, H. Laroui, Y. Yan, and D. Merlin The role and pathophysiological relevance of membrane transporter PepT1 in intestinal inflammation and inflammatory bowel disease Am. J. Physiol. Gastrointest. Liver Physiol. 302 2012 G484 492 10.1152/ajpgi.00477.2011
59. International Transporter Consortium, Giacomini, K.M., Huang, S.-M., Tweedie, D.J., Benet, L.Z., Brouwer, K.L.R., 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., 2010. Membrane transporters in drug development. Nat. Rev. Drug Discov. 9, 215-236 doi:10.1038/nrd3028.
60. D. Jappar, S.-P. Wu, Y. Hu, and D.E. Smith Significance and regional dependency of peptide transporter (PEPT) 1 in the intestinal permeability of glycylsarcosine: in situ single-pass perfusion studies in wild-type and Pept1 knockout mice Drug Metab. Dispos. 38 2010 1740 1746 10.1124/dmd.110.034025
61. M. Jin, T. Shimada, K. Yokogawa, M. Nomura, J. Ishizaki, Y. Piao, Y. Kato, A. Tsuji, and K.-I. Miyamoto Site-dependent contributions of P-glycoprotein and CYP3A to cyclosporin A absorption, and effect of dexamethasone in small intestine of mice Biochem. Pharmacol. 72 8 2006 1042 1050
62. G. Johannsson, R. Bergthorsdottir, A.G. Nilsson, H. Lennernas, T. Hedner, and S. Skrtic Improving glucocorticoid replacement therapy using a novel modified-release hydrocortisone tablet: a pharmacokinetic study Eur. J. Endocrinol. Eur. Fed. Endocr. Soc. 161 2009 119 130 10.1530/EJE-09-0170
63. B.M. Johnson, W. Chen, R.T. Borchardt, W.N. Charman, and C.J.H. Porter A kinetic evaluation of the absorption, efflux, and metabolism of verapamil in the autoperfused rat jejunum J. Pharmacol. Exp. Ther. 305 2003 151 158 10.1124/jpet.102.045328
64. T.N. Johnson, and M. Thomson Intestinal metabolism and transport of drugs in children: the effects of age and disease J. Pediatr. Gastroenterol. Nutr. 47 2008 3 10 10.1097/MPG0b013e31816a8cca
65. A. Kaddoumi, D. Fleisher, T. Heimbach, L.Y. Li, and S. Cole Factors influencing regional differences in intestinal absorption of UK-343,664 in rat: possible role in dose-dependent pharmacokinetics J. Pharm. Sci. 95 2006 435 445 10.1002/jps.20527
66. K. Katneni, S.A. Charman, and C.J.H. Porter Permeability assessment of poorly water-soluble compounds under solubilizing conditions: the reciprocal permeability approach J. Pharm. Sci. 95 2006 2170 2185 10.1002/jps.20687
67. O. Kis, J.A. Zastre, M.T. Hoque, S.L. Walmsley, and R. Bendayan Role of drug efflux and uptake transporters in atazanavir intestinal permeability and drug-drug interactions Pharm. Res. 30 2013 1050 1064 10.1007/s11095-012-0942-y
68. J.S. Lagas, C.W.N. Damen, R.A.B. van Waterschoot, D. Iusuf, J.H. Beijnen, and A.H. Schinkel P-glycoprotein, multidrug-resistance associated protein 2, Cyp3a, and carboxylesterase affect the oral availability and metabolism of vinorelbine Mol. Pharmacol. 82 2012 636 644 10.1124/mol.111.077099
69. K.-J. Lee, N. Johnson, J. Castelo, P.J. Sinko, G. Grass, K. Holme, and Y.-H. Lee Effect of experimental pH on the in vitro permeability in intact rabbit intestines and Caco-2 monolayer Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci. 25 2005 193 200 10.1016/j.ejps.2005.02.012
70. H. Lennernäs Regional intestinal drug permeation: biopharmaceutics and drug development Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci. 57 2014 333 341 10.1016/j.ejps.2013.08.025
71. H. Lennernäs, O. Ahrenstedt, R. Hällgren, L. Knutson, M. Ryde, and L.K. Paalzow Regional jejunal perfusion: a new in vivo approach to study oral drug absorption in man Pharm. Res. 9 1992 1243 1251
72. L.Y. Li, G.L. Amidon, S. Kim, T. Heimbach, F. Kesisoglou, J.T. Topliss, and D. Fleisher Intestinal metabolism promotes regional differences in apical uptake of indinavir: coupled effect of P-glycoprotein and cytochrome P450 3A on indinavir membrane permeability in rat J. Pharmacol. Exp. Ther. 301 2 2002 586 593
73. A. Lindahl, E. Krondahl, A.C. Grudén, A.L. Ungell, and H. Lennernäs Is the jejunal permeability in rats age-dependent? Pharm. Res. 14 1997 1278 1281
74. S. Liu, D. Tam, X. Chen, and K.S. Pang P-glycoprotein and an unstirred water layer barring digoxin absorption in the vascularly perfused rat small intestine preparation: induction studies with pregnenolone-16alpha-carbonitrile Drug Metab. Dispos. Biol. Fate Chem. 34 2006 1468 1479 10.1124/dmd.105.008227
75. C. MacLean, U. Moenning, A. Reichel, and G. Fricker Closing the gaps: a full scan of the intestinal expression of p-glycoprotein, breast cancer resistance protein, and multidrug resistance-associated protein 2 in male and female rats Drug Metab. Dispos. 36 7 2008 1249 1254
76. C. MacLean, U. Moenning, A. Reichel, and G. Fricker Regional absorption of fexofenadine in rat intestine Eur. J. Pharm. Sci. 41 5 2010 670 674
77. R. Mallants, K. Van Oosterwyck, L. Van Vaeck, R. Mols, E. De Clercq, and P. Augustijns Multidrug resistance-associated protein 2 (MRP2) affects hepatobiliary elimination but not the intestinal disposition of tenofovir disoproxil fumarate and its metabolites Xenobiotica 35 2005 1055 1066
78. C. Markopoulos, F. Thoenen, D. Preisig, M. Symillides, M. Vertzoni, N. Parrott, C. Reppas, and G. Imanidis Biorelevant media for transport experiments in the Caco -2 model to evaluate drug absorption in the fasted and the fed state and their usefulness Eur. J. Pharm. Biopharm. 2013 10.1016/j.ejpb.2013.10.017
79. M. Martignoni, G.M.M. Groothuis, and R. de Kanter Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction Exp. Opin. Drug Metab. Toxicol. 2 2006 875 894 10.1517/17425255.2.6.875
80. K. Masaki, M. Hashimoto, and T. Imai Intestinal first-pass metabolism via carboxylesterase in rat jejunum and ileum Drug Metab. Dispos. Biol. Fate Chem. 35 2007 1089 1095 10.1124/dmd.106.013862
81. X. Ma, C. Cheung, K.W. Krausz, Y.M. Shah, T. Wang, J.R. Idle, and F.J. Gonzalez A double transgenic mouse model expressing human pregnane X receptor and cytochrome P450 3A4 Drug Metab. Dispos. 36 12 2008 2506 2512
82. C. Meaney, and C. O'Driscoll Mucus as a barrier to the permeability of hydrophilic and lipophilic compounds in the absence and presence of sodium taurocholate micellar systems using cell culture models Eur. J. Pharm. Sci. 8 1999 167 175 10.1016/S0928-0987(99)00007-X
83. Y. Meier, J.J. Eloranta, J. Darimont, M.G. Ismair, C. Hiller, M. Fried, G.A. Kullak-Ublick, and S.R. Vavricka Regional distribution of solute carrier mRNA expression along the human intestinal tract Drug metabolism and Disposition 35 4 2007 590 594
84. R. Mellaerts, R. Mols, P. Kayaert, P. Annaert, J. Van Humbeeck, G. Van den Mooter, J.A. Martens, and P. Augustijns Ordered mesoporous silica induces pH-independent supersaturation of the basic low solubility compound itraconazole resulting in enhanced transepithelial transport Int. J. Pharm. 357 2008 169 179 10.1016/j.ijpharm.2008.01.049
85. J.M. Miller, A. Beig, R.A. Carr, J.K. Spence, and A. Dahan A win-win solution in oral delivery of lipophilic drugs: supersaturation via amorphous solid dispersions increases apparent solubility without sacrifice of intestinal membrane permeability Mol. Pharm. 9 2012 2009 2016 10.1021/mp300104s
86. J.M. Miller, A. Beig, B.J. Krieg, R.A. Carr, T.B. Borchardt, G.E. Amidon, G.L. Amidon, and A. Dahan The solubility-permeability interplay: mechanistic modeling and predictive application of the impact of micellar solubilization on intestinal permeation Mol. Pharm. 8 2011 1848 1856 10.1021/mp200181v
87. D. Mitschke, A. Reichel, G. Fricker, and U. Moenning Characterization of cytochrome P450 protein expression along the entire length of the intestine of male and female rats Drug Metab. Dispos. Biol. Fate Chem. 36 2008 1039 1045 10.1124/dmd.107.019687
88. R. Mols, J. Brouwers, A.H. Schinkel, P. Annaert, and P. Augustijns Intestinal perfusion with mesenteric blood sampling in wild-type and knockout mice: evaluation of a novel tool in biopharmaceutical drug profiling Drug metabolism and disposition 37 6 2009 1334 1337
89. D.R. Mudra, and R.T. Borchardt Absorption barriers in the rat intestinal mucosa: 1. Application of an in situ perfusion model to simultaneously assess drug permeation and metabolism J. Pharm. Sci. 99 2010 982 998 10.1002/jps.21912
90. D.R. Mudra, K.E. Desino, and P.V. Desai In silico, in vitro and in situ models to assess interplay between CYP3A and P-gp Curr. drug metab. 12 8 2011 750 773
91. S. Oguri, M. Kumazaki, R. Kitou, H. Nonoyama, and N. Tooda Elucidation of intestinal absorption of d,l-amino acid enantiomers and aging in rats Biochim. Biophys. Acta 1472 1999 107 114
92. K. Ohura, T. Soejima, R. Nogata, Y. Adachi, S. Ninomiya, and T. Imai Effect of intestinal first-pass hydrolysis on the oral bioavailability of an ester prodrug of fexofenadine J. Pharm. Sci. 101 2012 3264 3274 10.1002/jps.23182
93. N. Okudaira, T. Tatebayashi, G.C. Speirs, I. Komiya, and Y. Sugiyama A study of the intestinal absorption of an ester-type prodrug, ME3229, in rats: active efflux transport as a cause of poor bioavailability of the active drug J. Pharmacol. Exp. Ther. 294 2000 580 587
94. F.G. Poelma, R. Breäs, and J.J. Tukker Intestinal absorption of drugs. III. The influence of taurocholate on the disappearance kinetics of hydrophilic and lipophilic drugs from the small intestine of the rat Pharm. Res. 7 1990 392 397
95. F.G. Poelma, R. Breäs, J.J. Tukker, and D.J. Crommelin Intestinal absorption of drugs. The influence of mixed micelles on on the disappearance kinetics of drugs from the small intestine of the rat J. Pharm. Pharmacol. 43 1991 317 324
96. K.S.R. Raju, S.P. Singh, and I. Taneja Investigation of the functional role of P-glycoprotein in limiting the oral bioavailability of lumefantrine Antimicrob. Agents Chemother. 58 2014 489 494 10.1128/AAC.01382- 13
97. Z. Rong, Y. Xu, C. Zhang, D. Xiang, X. Li, and D. Liu Evaluation of intestinal absorption of amtolmetin guacyl in rats: breast cancer resistant protein as a primary barrier of oral bioavailability Life Sci. 92 2013 245 251 10.1016/j.lfs.2012.12.010
98. M. Sababi, O. Borgå, and U. Hultkvist-Bengtsson The role of P-glycoprotein in limiting intestinal regional absorption of digoxin in rats Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci. 14 2001 21 27
99. L. Salphati, and L.Z. Benet Metabolism of digoxin and digoxigenin digitoxosides in rat liver microsomes: involvement of cytochrome P4503A Xenobiotica Fate Foreign Compd. Biol. Syst. 29 1999 171 185 10.1080/004982599238722
100. R. Sandström, and H. Lennernäs Repeated oral rifampicin decreases the jejunal permeability of R/S-verapamil in rats Drug Metab. Dispos. Biol. Fate Chem. 27 1999 951 955
101. L.S. Schanker, D.J. Tocco, B.B. Brodie, and C.A. Hogben Absorption of drugs from the rat small intestine J. Pharmacol. Exp. Ther. 123 1958 81 88
102. N.G. Schipper, K.M. Vârum, P. Stenberg, G. Ocklind, H. Lennernäs, and P. Artursson Chitosans as absorption enhancers of poorly absorbable drugs. 3. Influence of mucus on absorption enhancement Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci. 8 1999 335 343
103. P. Schmiedlin- Ren, K.E. Thummel, J.M. Fisher, M.F. Paine, K.S. Lown, and P.B. Watkins Expression of enzymatically active CYP3A4 by Caco-2 cells grown on extracellular matrix-coated permeable supports in the presence of 1alpha,25-dihydroxyvitamin D3 Mol. Pharmacol. 51 1997 741 754
104. E.G. Schuetz, D.R. Umbenhauer, K. Yasuda, C. Brimer, L. Nguyen, M.V. Relling, J.D. Schuetz, and A.H. Schinkel Altered expression of hepatic cytochromes P-450 in mice deficient in one or more mdr1 genes Mol. Pharmacol. 57 2000 188 197
105. A.L.A. Sesink, I.C.W. Arts, V.C.J. de Boer, P. Breedveld, J.H.M. Schellens, P.C.H. Hollman, and F.G.M. Russel Breast cancer resistance protein (Bcrp1/Abcg2) limits net intestinal uptake of quercetin in rats by facilitating apical efflux of glucuronides Mol. Pharmacol. 67 1999 1999 2006 10.1124/mol.104.009753
106. Y. Shirasaka, T. Sakane, and S. Yamashita Effect of P-glycoprotein expression levels on the concentration-dependent permeability of drugs to the cell membrane J. Pharm. Sci. 97 2008 553 565 10.1002/jps.21114
107. Y. Shirasaka, K. Suzuki, M. Shichiri, T. Nakanishi, and I. Tamai Intestinal absorption of HMG-CoA reductase inhibitor pitavastatin mediated by organic anion transporting polypeptide and P-glycoprotein/multidrug resistance 1 Drug Metab. Pharmacokinet 26 2011 171 179
108. Å Sjöberg, M. Lutz, C. Tannergren, C. Wingolf, A. Borde, and A.-L. Ungell Comprehensive study on regional human intestinal permeability and prediction of fraction absorbed of drugs using the Ussing chamber technique Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci. 48 2013 166 180 10.1016/j.ejps.2012.10.007
109. J. Stappaerts, P. Annaert, and P. Augustijns Site dependent intestinal absorption of darunavir and its interaction with ketoconazole Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci. 49 2013 51 56 10.1016/j.ejps.2013.01.015
110. J. Stappaerts, S. Fattah, P. Annaert, and P. Augustijns Hepatobiliary and intestinal elimination of darunavir in an integrated preclinical rat model Xenobiotica Fate Foreign Compd. Biol. Syst. 44 2014 489 497 10.3109/00498254.2013.861541
111. J. Stappaerts, B. Wuyts, J. Tack, P. Annaert, and P. Augustijns Human and simulated intestinal fluids as solvent systems to explore food effects on intestinal solubility and permeability Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci. 63C 2014 178 186 10.1016/j.ejps.2014.07
112. S. Stegemann, F. Leveiller, D. Franchi, H. de Jong, and H. Lindén When poor solubility becomes an issue: from early stage to proof of concept Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci. 31 2007 249 261 10.1016/j.ejps.2007.05.110
113. R.H. Stephens, C.A. O'Neill, A. Warhurst, G.L. Carlson, M. Rowland, and G. Warhurst Kinetic profiling of P-glycoprotein-mediated drug efflux in rat and human intestinal epithelia J. Pharmacol. Exp. Ther. 296 2 2001 584 591
114. K. Stoeckel, W. Hofheinz, J.P. Laneury, P. Duchene, S. Shedlofsky, and R.A. Blouin Stability of cephalosporin prodrug esters in human intestinal juice: implications for oral bioavailability Antimicrob. Agents Chemother. 42 1998 2602 2606
115. S.C. Sutton, M.T. Rinaldi, and K.E. Vukovinsky Comparison of the gravimetric, phenol red, and 14C-PEG-3350 methods to determine water absorption in the rat single-pass intestinal perfusion model AAPS PharmSci. 3 2001 E25
116. Takara, K., Ohnishi, N., Horibe, S., Yokoyama, T., 2003. Expression profiles of drug-metabolizing enzyme CYP3A and drug efflux transporter multidrug resistance 1 subfamily mRNAS in small intestine, 1235-1239.
117. S. Tamura, A. Ohike, R. Ibuki, G.L. Amidon, and S. Yamashita Tacrolimus is a class II low-solubility high-permeability drug: the effect of P-glycoprotein efflux on regional permeability of tacrolimus in rats J. Pharm. Sci. 91 2002 719 729
118. S. Tamura, Y. Tokunaga, R. Ibuki, G.L. Amidon, H. Sezaki, and S. Yamashita The site-specific transport and metabolism of tacrolimus in rat small intestine J. Pharmacol. Exp. Ther. 306 2003 310 316 10.1124/jpet.103.050716
119. S.C. Tang, J.J.M.A. Hendrikx, J.H. Beijnen, and A.H. Schinkel Genetically modified mouse models for oral drug absorption and disposition Curr. Opin. Pharmacol. 13 2013 853 858 10.1016/j.coph.2013.08.011
120. C. Tannergren, A. Bergendal, H. Lennernäs, and B. Abrahamsson Toward an increased understanding of the barriers to colonic drug absorption in humans: implications for early controlled release candidate assessment Mol. Pharm. 6 2009 60 73 10.1021/mp800261a
121. A.G. Thombre Assessment of the feasibility of oral controlled release in an exploratory development setting Drug Discov. Today 10 2005 1159 1166 10.1016/S1359-6446(05)03551-8
122. K.E. Thummel, C. Brimer, K. Yasuda, J. Thottassery, T. Senn, Y. Lin, H. Ishizuka, E. Kharasch, J. Schuetz, and E. Schuetz Transcriptional control of intestinal cytochrome P-4503A by 1α,25-dihydroxy vitamin D3 Mol. Pharmacol. 60 2001 1399 1406 10.1124/mol.60.6.1399
123. H.H. Usansky, P. Hu, and P.J. Sinko Differential roles of P-glycoprotein, multidrug resistance-associated protein 2, and CYP3A on saquinavir oral absorption in Sprague-Dawley rats Drug Metab. Dispos. 36 5 2008 863 869
124. B. Valenzuela, A. Nácher, P. Ruiz-Carretero, A. Martín-Villodre, G. López-Carballo, and D. Barettino Profile of P-glycoprotein distribution in the rat and its possible influence on the salbutamol intestinal absorption process J. Pharm. Sci. 93 2004 1641 1648 10.1002/jps.20071
125. J. Van Gelder, S. Deferme, P. Annaert, L. Naesens, E. De Clercq, G. Van den Mooter, R. Kinget, and P. Augustijns Increased absorption of the antiviral ester prodrug tenofovir disoproxil in rat ileum by inhibiting its intestinal metabolism Drug Metab. Dispos. Biol. Fate Chem. 28 2000 1394 1396
126. J. Van Gelder, M. Shafiee, E. De Clercq, F. Penninckx, G. Van den Mooter, R. Kinget, and P. Augustijns Species-dependent and site-specific intestinal metabolism of ester prodrugs Int. J. Pharm. 205 2000 93 100
127. R.A.B. Van Waterschoot, and A.H. Schinkel A critical analysis of the interplay between cytochrome P450 3A and P-glycoprotein: recent insights from knockout and transgenic mice Pharmacol. Rev. 63 2011 390 410 10.1124/pr.110.002584
128. M.V. Varma, C.M. Ambler, M. Ullah, C.J. Rotter, H. Sun, J. Litchfield, K.S. Fenner, and A.F. El-Kattan Targeting intestinal transporters for optimizing oral drug absorption Curr. Drug Metab. 11 2010 730 742
129. M. Vertzoni, N. Fotaki, E. Kostewicz, E. Stippler, C. Leuner, E. Nicolaides, J. Dressman, and C. Reppas Dissolution media simulating the intralumenal composition of the small intestine: physiological issues and practical aspects J. Pharm. Pharmacol. 56 2004 453 462 10.1211/0022357022935
130. D. Wagner, H. Spahn-Langguth, A. Hanafy, A. Koggel, and P. Langguth Intestinal drug efflux: formulation and food effects Adv. drug delivery Rev. 50 2001 S13 S31
131. H. Wang, H. Kawashima, and H.W. Strobel cDNA cloning of a novel CYP3A from rat brain Biochem. Biophys. Res. Commun. 221 1996 157 162 10.1006/bbrc.1996.0562
132. H.D. Williams, P. Sassene, K. Kleberg, J.-C. Bakala-N'Goma, M. Calderone, V. Jannin, A. Igonin, A. Partheil, D. Marchaud, E. Jule, J. Vertommen, M. Maio, R. Blundell, H. Benameur, F. Carrière, A. Müllertz, C.J.H. Porter, and C.W. Pouton Toward the establishment of standardized in vitro tests for lipid-based formulations, part 1: method parameterization and comparison of in vitro digestion profiles across a range of representative formulations J. Pharm. Sci. 101 2012 3360 3380 10.1002/jps.23205
133. H.D. Williams, N.L. Trevaskis, S.A. Charman, R.M. Shanker, W.N. Charman, C.W. Pouton, and C.J.H. Porter Strategies to address low drug solubility in discovery and development Pharmacol. Rev. 65 2013 315 499
134. H.D. Williams, N.L. Trevaskis, Y.Y. Yeap, M.U. Anby, C.W. Pouton, and C.J.H. Porter Lipid-based formulations and drug supersaturation: harnessing the unique benefits of the lipid digestion/absorption pathway Pharm. Res. 30 2013 2976 2992 10.1007/s11095-013-1126-0
135. T.M. Willson, and S.A. Kliewer PXR, CAR and drug metabolism Nat. Rev. Drug Discov. 1 2002 259 266 10.1038/nrd753
136. B. Yang, and D.E. Smith Significance of peptide transporter 1 in the intestinal permeability of valacyclovir in wild-type and PepT1 knockout mice Drug Metab. Dispos. Biol. Fate Chem. 41 2013 608 614 10.1124/dmd.112.049239
137. Z. Yang, W. Zhu, S. Gao, T. Yin, W. Jiang, and M. Hu Breast cancer resistance protein (ABCG2) determines distribution of genistein phase II metabolites: reevaluation of the roles of ABCG2 in the disposition of genistein Drug Metab. Dispos. Biol. Fate Chem. 40 2012 1883 1893 10.1124/dmd.111.043901
138. K. Yano, Y. Masaoka, M. Kataoka, S. Sakuma, and S. Yamashita Mechanisms of membrane transport of poorly soluble drugs: role of micelles in oral absorption processes J. Pharm. Sci. 99 2010 1336 1345 10.1002/jps.21919
139. Y.Y. Yeap, N.L. Trevaskis, and C.J.H. Porter The potential for drug supersaturation during intestinal processing of lipid-based formulations may be enhanced for basic drugs Mol. Pharm. 10 2013 2601 2615 10.1021/mp400035z
140. Y.Y. Yeap, N.L. Trevaskis, and C.J.H. Porter Lipid absorption triggers drug supersaturation at the intestinal unstirred water layer and promotes drug absorption from mixed micelles Pharm. Res. 30 2013 3045 3058 10.1007/s11095-013-1104-6
141. Y.Y. Yeap, N.L. Trevaskis, T. Quach, P. Tso, W.N. Charman, and C.J.H. Porter Intestinal bile secretion promotes drug absorption from lipid colloidal phases via induction of supersaturation Mol. Pharm. 10 2013 1874 1889 10.1021/mp3006566
142. H. Yuasa, N. Soga, Y. Kimura, and J. Watanabe Effect of aging on the intestinal transport of hydrophilic drugs in the rat small intestine Biol. Pharm. Bull. 20 1997 1188 1192
143. M.J. Zamek- Gliszczynski, D.W. Bedwell, J.Q. Bao, and J.W. Higgins Characterization of SAGE Mdr1a (P-gp), Bcrp, and Mrp2 knockout rats using loperamide, paclitaxel, sulfasalazine, and carboxydichlorofluorescein pharmacokinetics Drug Metab. Dispos. Biol. Fate Chem. 40 2012 1825 1833 10.1124/dmd.112.046508
144. M. Zur, M. Gasparini, O. Wolk, G.L. Amidon, and A. Dahan The low/high BCS permeability class boundary: physicochemical comparison of metoprolol and labetalol Mol. Pharm. 11 2014 1707 1714 10.1021/mp500152y
145. M. Zur, A.S. Hanson, and A. Dahan The complexity of intestinal permeability: assigning the correct BCS classification through careful data interpretation Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci. 61 2014 11 17 10.1016/j.ejps.2013.11.007