Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist

Science Translational Medicine

Volumn 10, Issue 468, 2018, Pages

  Buckley, Stephen T ^a   Bækdal, Tine A ^a   Vegge, Andreas ^a   Maarbjerg, Stine J ^a   Pyke, Charles ^a   Ahnfelt Rønne, Jonas ^a   Madsen, Kim G ^a   Schéele, Susanne G ^a   Alanentalo, Tomas ^a   Kirk, Rikke K ^a   Pedersen, Betty L ^a   Skyggebjerg, Rikke B ^a   Benie, Andrew J ^a   Strauss, Holger M ^a   Wahlund, Per Olof ^a   Bjerregaard, Simon ^a   Farkas, Erzsébet ^b   Fekete, Csaba ^b,c   Søndergaard, Flemming L ^a   Borregaard, Jeanett ^a   Hartoft Nielsen, Marie Louise ^a   Knudsen, Lotte Bjerre ^a   more..

^a NOVO NORDISK A S   (Denmark)

^b INSTITUTE OF EXPERIMENTAL MEDICINE   (Hungary)

^c TUFTS MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

OCTANOIC ACID DERIVATIVE; PLACEBO; SEMAGLUTIDE; SODIUM N [8 (2 HYDROXYBENZOYL)AMINOCAPRYLATE]; UNCLASSIFIED DRUG; GLUCAGON LIKE PEPTIDE; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 1 RECEPTOR;

ADULT; AGED; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG FORMULATION; ENZYMATIC DEGRADATION; HUMAN; HUMAN EXPERIMENT; INTESTINE ABSORPTION; MALE; NONHUMAN; NORMAL HUMAN; OPEN STUDY; PARALLEL DESIGN; PRECLINICAL STUDY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE; STOMACH ABSORPTION; TABLET; TABLET SURFACE; TIGHT JUNCTION; ADOLESCENT; ANIMAL; CELL MEMBRANE; DOG; DRUG EFFECT; EPITHELIUM CELL; METABOLISM; MIDDLE AGED; ORAL DRUG ADMINISTRATION; PH; PHYSIOLOGY; RAT; STOMACH; STOMACH MUCOSA; TIME FACTOR; ULTRASTRUCTURE; YOUNG ADULT;

ADMINISTRATION, ORAL; ADOLESCENT; ADULT; AGED; ANIMALS; CELL MEMBRANE; DOGS; EPITHELIAL CELLS; GASTRIC MUCOSA; GLUCAGON-LIKE PEPTIDE 1; GLUCAGON-LIKE PEPTIDE-1 RECEPTOR; GLUCAGON-LIKE PEPTIDES; HUMANS; HYDROGEN-ION CONCENTRATION; INTESTINAL ABSORPTION; MALE; MIDDLE AGED; RATS; STOMACH; TIME FACTORS; YOUNG ADULT;

EID: 85056619309     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.aar7047     Document Type: Article

References (42)

1. J. J. Meier, GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat. Rev. Endocrinol. 8, 728-742 (2012).
2. J. J. Meier, J. Rosenstock, A. Hincelin-Mery, C. Roy-Duval, A. Delfolie, H. V. Coester, B. A. Menge, T. Forst, C. Kapitza, Contrasting effects of lixisenatide and liraglutide on postprandial glycemic control, gastric emptying, and safety parameters in patients with type 2 diabetes on optimized insulin glargine with or without metformin: A randomized, open-label trial. Diabetes Care 38, 1263-1273 (2015).
3. A. Secher, J. Jelsing, A. F. Baquero, J. Hecksher-Sorensen, M. A. Cowley, L. S. Dalboge, G. Hansen, K. L. Grove, C. Pyke, K. Raun, L. Schaffer, M. Tang-Christensen, S. Verma, B. M. Witgen, N. Vrang, L. Bjerre Knudsen, The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss. J. Clin. Invest. 124, 4473-4488 (2014).
4. X. Pi-Sunyer, A. Astrup, K. Fujioka, F. Greenway, A. Halpern, M. Krempf, D. C. W. Lau, C. W. le Roux, R. Violante Ortiz, C. B. Jensen, J. P. H. Wilding; SCALE Obesity and Prediabetes NN8022-1839 Study Group, A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N. Engl. J. Med. 373, 11-22 (2015).
5. S. P. Marso, G. H. Daniels, K. Brown-Frandsen, P. Kristensen, J. F. E. Mann, M. A. Nauck, S. E. Nissen, S. Pocock, N. R. Poulter, L. S. Ravn, W. M. Steinberg, M. Stockner, B. Zinman, R. M. Bergenstal, J. B. Buse; LEADER Steering Committee, LEADER Trial Investigators, Liraglutide and cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 375, 311-322 (2016).
6. S. P. Marso, S. C. Bain, A. Consoli, F. G. Eliaschewitz, E. Jodar, L. A. Leiter, I. Lingvay, J. Rosenstock, J. Seufert, M. L. Warren, V. Woo, O. Hansen, A. G. Holst, J. Pettersson, T. Vilsboll; SUSTAIN-6 Investigators, Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 375, 1834-1844 (2016).
7. J. A. Lovshin, D. J. Drucker, Incretin-based therapies for type 2 diabetes mellitus. Nat. Rev. Endocrinol. 5, 262-269 (2009).
8. J. Lau, P. Bloch, L. Schaffer, I. Pettersson, J. Spetzler, J. Kofoed, K. Madsen, L. B. Knudsen, J. McGuire, D. B. Steensgaard, H. M. Strauss, D. X. Gram, S. M. Knudsen, F. S. Nielsen, P. Thygesen, S. Reedtz-Runge, T. Kruse, Discovery of the once-weekly glucagon-like peptide-1 (GLP-1) analogue semaglutide. J. Med. Chem. 58, 7370-7380 (2015).
9. C. E. Cooke, H. Y. Lee, Y. P. Tong, S. T. Haines, Persistence with injectable antidiabetic agents in members with type 2 diabetes in a commercial managed care organization. Curr. Med. Res. Opin. 26, 231-238 (2010).
10. T. A. Aguirre, D. Teijeiro-Osorio, M. Rosa, I. S. Coulter, M. J. Alonso, D. J. Brayden, Current status of selected oral peptide technologies in advanced preclinical development and in clinical trials. Adv. Drug Deliv. Rev. 106, 223-241 (2016).
11. M. Davies, T. R. Pieber, M.-L. Hartoft-Nielsen, O. K. H. Hansen, S. Jabbour, J. Rosenstock, Effect of oral semaglutide compared with placebo and subcutaneous semaglutide on glycemic control in patients with type 2 diabetes: A randomized clinical trial. J. Am. Med. Assoc. 318, 1460-1470 (2017).
12. M. Tomita, M. Hayashi, S. Awazu, Absorption-enhancing mechanism of EDTA, caprate, and decanoylcarnitine in Caco-2 cells. J. Pharm. Sci. 85, 608-611 (1996).
13. T. M. Frederiksen, P. Sonderby, L. A. Ryberg, P. Harris, J. T. Bukrinski, A. M. Scharff-Poulsen, M. N. Elf-Lind, G. H. Peters, Oligomerization of a glucagon-like peptide 1 analog: Bridging experiment and simulations. Biophys. J. 15, 1202-1213 (2015).
14. D. W. Piper, B. H. Fenton, pH stability and activity curves of pepsin with special reference to their clinical importance. Gut 6, 506-508 (1965).
15. A. Wettergren, M. Wojdemann, S. Meisner, F. Stadil, J. J. Holst, The inhibitory effect of glucagon-like peptide-1 (GLP-1) 7-36 amide on gastric acid secretion in humans depends on an intact vagal innervation. Gut 40, 597-601 (1997).
16. H. Lennernas, Regional intestinal drug permeation: Biopharmaceutics and drug development. Eur. J. Pharm. Sci. 57, 333-341 (2014).
17. J. Van Den Abeele, J. Rubbens, J. Brouwers, P. Augustijns, The dynamic gastric environment and its impact on drug and formulation behaviour. Eur. J. Pharm. Sci. 96, 207-231 (2017).
18. S. Maher, R. J. Mrsny, D. J. Brayden, Intestinal permeation enhancers for oral peptide delivery. Adv. Drug Deliv. Rev. 106, 277-319 (2016).
19. M. A. Karsdal, I. Byrjalsen, B. J. Riis, C. Christiansen, Optimizing bioavailability of oral administration of small peptides through pharmacokinetic and pharmacodynamic parameters: The effect of water and timing of meal intake on oral delivery of salmon calcitonin. BMC Clin. Pharmacol. 8, 5 (2008).
20. M. A. Karsdal, I. Byrjalsen, M. Azria, M. Arnold, L. Choi, B. J. Riis, C. Christiansen, Influence of food intake on the bioavailability and efficacy of oral calcitonin. Br. J. Clin. Pharmacol. 67, 413-420 (2009).
21. Y.-H. Lee, B. A. Perry, J. P. Sutyak, W. Stern, P. J. Sinko, Regional differences in intestinal spreading and pH recovery and the impact on salmon calcitonin absorption in dogs. Pharm. Res. 17, 284-290 (2000).
22. J. Worsoe, L. Fynne, T. Gregersen, V. Schlageter, L. A. Christensen, J. F. Dahlerup, N. J. M. Rijkhoff, S. Laurberg, K. Krogh, Gastric transit and small intestinal transit time and motility assessed by a magnet tracking system. BMC Gastroenterol. 11, 145 (2011).
23. K. Whitehead, Z. Shen, S. Mitragotri, Oral delivery of macromolecules using intestinal patches: Applications for insulin delivery. J. Control. Release 98, 37-45 (2004).
24. B. Bittner, C. McIntyre, P. Jordan, J. Schmidt, Drug-drug interaction study between a novel oral ibandronate formulation and metformin. Arzneimittelforschung 61, 707-713 (2011).
25. C. McIntyre, J. Schmidt, M. C. Castelli, B. Bittner, Study on the impact of SNAC (sodium N-[8-(2-hydroxybenzoyl) amino] caprylate) on the bioavailability of ibandronate (IBN) in postmenopausal women. J. Drug Delivery Sci. Technol. 21, 521-525 (2011).
26. J. Wang, V. Yadav, A. L. Smart, S. Tajiri, A. W. Basit, Toward oral delivery of biopharmaceuticals: An assessment of the gastrointestinal stability of 17 peptide drugs. Mol. Pharm. 12, 966-973 (2015).
27. S. H. Welling, F. Hubalek, J. Jacobsen, D. J. Brayden, U. L. Rahbek, S. T. Buckley, The role of citric acid in oral peptide and protein formulations: Relationship between calcium chelation and proteolysis inhibition. Eur. J. Pharm. Biopharm. 86, 544-551 (2014).
28. A. Leone-Bay, D. R. Paton, B. Variano, H. Leipold, T. Rivera, J. Miura-Fraboni, R. A. Baughman, N. Santiago, Acylated non-α-amino acids as novel agents for the oral delivery of heparin sodium, USP. J. Control Release 50, 41-49 (1998).
29. M. Nazari, M. Kurdi, H. Heerklotz, Classifying surfactants with respect to their effect on lipid membrane order. Biophys. J. 102, 498-506 (2012).
30. D. J. Brayden, J. Gleeson, E. G. Walsh, A head-to-head multi-parametric high content analysis of a series of medium chain fatty acid intestinal permeation enhancers in Caco-2 cells. Eur. J. Pharm. Biopharm. 88, 830-839 (2014).
31. S. Trier, L. Linderoth, S. Bjerregaard, T. L. Andresen, U. L. Rahbek, Acylation of glucagon-like peptide-2: Interaction with lipid membranes and in vitro intestinal permeability. PLOS ONE 9, e109939 (2014).
32. D. Malkov, R. Angelo, H.-Z. Wang, E. Flanders, H. Tang, I. Gomez-Orellana, Oral delivery of insulin with the eligen technology: Mechanistic studies. Curr. Drug Deliv. 2, 191-197 (2005).
33. S.-J. Wu, J. R. Robinson, Transcellular and lipophilic complex-enhanced intestinal absorption of human growth hormone. Pharm. Res. 16, 1266-1272 (1999).
34. X. Wang, S. Maher, D. J. Brayden, Restoration of rat colonic epithelium after in situ intestinal instillation of the absorption promoter, sodium caprate. Ther. Deliv. 1, 75-82 (2010).
35. S. Tuvia, D. Pelled, K. Marom, P. Salama, M. Levin-Arama, I. Karmeli, G. H. Idelson, I. Landau, R. Mamluk, A novel suspension formulation enhances intestinal absorption of macromolecules via transient and reversible transport mechanisms. Pharm. Res. 31, 2010-2021 (2014).
36. E. R. Lacy, S. Ito, Rapid epithelial restitution of the rat gastric mucosa after ethanol injury. Lab. Invest. 51, 573-583 (1984).
37. S. Ito, E. R. Lacy, M. J. Rutten, J. Critchlow, W. Silen, Rapid repair of injured gastric mucosa. Scand. J. Gastroenterol. Suppl. 101, 87-95 (1984).
38. E. R. Lacy, G. P. Morris, M. M. Cohen, Rapid repair of the surface epithelium in human gastric mucosa after acute superficial injury. J. Clin. Gastroenterol. 17, S125-S135 (1993).
39. G. L. Eastwood, Effect of pH on bile salt injury to mouse gastric mucosa. A light- and electron-microscopic study. Gastroenterology 68, 1456-1465 (1975).
40. U.S. Food and Drug Administration, Guidance for industry: Food-effect bioavailability and fed bioequivalence studies, December 2002. www.fda.gov/downloads/drugs/ guidancecomplianceregulatoryinformation/guidances/ucm070241.pdf.
41. European Medicines Agency, Committee for human medicinal products: Guideline on the investigation of drug interactions, 21 June 2012. www.ema.europa.eu/docs/en-GB/ document-library/Scientific-guideline/2012/07/WC500129606.pdf.
42. W. Weitschies, H. Blume, H. Monnikes, Magnetic marker monitoring: High resolution real-time tracking of oral solid dosage forms in the gastrointestinal tract. Eur. J. Pharm. Biopharm. 74, 93-101 (2010).