Prodrug approach for α(IIb)β3-peptidomimetic antagonists to enhance their transport in monolayers of a human intestinal cell line (Caco-2): Comparison of in vitro and in vivo data

Pharmaceutical Research

Volumn 16, Issue 10, 1999, Pages 1527-1533

  Kamm, Walter ^a   Raddatz, Peter ^b   Gante, Joachim ^b   Kissel, Thomas ^a  

^a PHILIPPS UNIVERSITY MARBURG   (Germany)

^b MERCK KGAA   (Germany)

Author keywords

(IIb) 3 antagonists; Caco 2 cells; Efflux; Peptidomimetic transport and metabolism; Prodrugs

Indexed keywords

4 [[3 [4 [IMINO[(METHOXYCARBONYL)AMINO]METHYL]PHENYL] 2 OXO 5 OXAZOLIDINYL]METHYL] 1 PIPERAZINEACETIC ACID ETHYL ESTER; ANTITHROMBOCYTIC AGENT; EMD 80200; EMD 81714; EMD 85900; EMD 87313; EMD 87314; UNCLASSIFIED DRUG; BUFFER; FIBRINOGEN RECEPTOR; OCTANOL; PRODRUG;

ANIMAL EXPERIMENT; ARTICLE; CELL MEMBRANE TRANSPORT; DRUG BIOAVAILABILITY; DRUG CONFORMATION; DRUG FORMULATION; DRUG PENETRATION; DRUG SOLUBILITY; DRUG UPTAKE; GUINEA PIG; HUMAN; HUMAN CELL; INTESTINE CELL; LIPID SOLUBILITY; MONKEY; NONHUMAN; ORAL DRUG ADMINISTRATION; PRIORITY JOURNAL; THROMBOCYTE AGGREGATION INHIBITION; ANIMAL; BIOTRANSFORMATION; CELL STRAIN CACO 2; CHEMISTRY; DRUG ANTAGONISM; DRUG EFFECT; ELECTROPHYSIOLOGY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IN VITRO STUDY; INTESTINE ABSORPTION; MACACA; PHYSICAL CHEMISTRY; SOLUBILITY; THROMBOCYTE AGGREGATION; TRANSPORT AT THE CELLULAR LEVEL; ULTRAVIOLET SPECTROPHOTOMETRY;

ANIMALS; BIOLOGICAL TRANSPORT; BIOTRANSFORMATION; BUFFERS; CACO-2 CELLS; CHEMISTRY, PHYSICAL; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; ELECTROPHYSIOLOGY; GUINEA PIGS; HUMANS; INTESTINAL ABSORPTION; MACACA FASCICULARIS; OCTANOLS; PLATELET AGGREGATION; PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX; PRODRUGS; SOLUBILITY; SPECTROPHOTOMETRY, ULTRAVIOLET;

EID: 0033210969     PISSN: 07248741     EISSN: None     Source Type: Journal    
DOI: 10.1023/A:1015044318650     Document Type: Article

References (31)

1. W. H. Frishman, B. Burns, B. Atac, N. Alturk, B. Altajar, and K. Lerrick. Novel antiplatelet therapies for treatment of patients with ischemic heart disease: inhibitors of the platelet glycoprotein IIb/IIIa integrin receptor. Am. Heart J. 130:877-892 (1995).
2. E. F. Plow, M. D. Pierschbacher, E. Ruoslahti, G. Marguerie, and M. H. Ginsberg. Arginyl-glycyl-aspartic acid sequences and fibrinogen binding to platelets. Blood 70: 110-115 (1987).
3. D. Cox, T. Aoki, J. Seki, Y. Motoyama, and K. Yoshida. The pharmacology of the integrins.Med. Res. Rev. 14:195-228 (1994).
4. P. Artursson. Cell cultures as models for drug absorption across the intestinal mucosa. Crit. Rev. Ther. Drug Carr. Syst. 8:305-330 (1991).
5. J. Gante, H. Juraszyk, P. Raddatz, H. Wurziger, S. Bernotat-Danielowski, G. Melzer, and F. Rippmann. New antithrombotic RGD-mimetics with high bioavailability. Biorg. Med. Chem. Lett. 6:2425-2430 (1996).
6. J. Gante, H. Juraszyk, P. Raddatz, H. Wurziger, S. Bernotat-Danielowski, G. Melzer, and F. Rippmann. New peptidomimetics in the chemistry of fibrinogen receptor antagonists. Lett. Pept. Sci. 2:135-140 (1995).
7. E. Walter, T. Kissel, M. Reers, G. Dickneite, D. Hoffmann, and W. Stüber. Transepithelial transport properties of peptidomimetic thrombin inhibitors in monolayers of a human intestinal cell line (Caco-2) and their correlation to in vivo data. Pharm. Res. 12:360-365 (1995).
8. U. Werner, T. Kissel, and W. Stüber. Effect of peptide structure on transport properties of seven thyrotropin releasing hormone (TRH) analogues in a human intestinal cell line (Caco-2). Pharm. Res. 14:246-250 (1997).
9. A. R. Hilgers, R. A. Conradi, and P. S. Burton. Caco-2 cell monolayers as a model for drug transport across the intestinal mucosa. Pharm. Res. 7:902-910 (1990).
10. G. V. R. Born. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 194:927-929 (1962).
11. D. Loew and H. Vinazzer. Influence of simultaneous administration of low-dose heparin and acetylsalicylic acid on blood coagulation and platelet functions.Haemostasis 3:319-328 (1974).
12. U. Werner, T. Kissel, and M. Reers. Effects of permeation enhancers on the transport of a peptidomimetic thrombin inhibitor (CRC 220) in a human intestinal cell line (Caco-2). Pharm. Res. 13:1219-1227 (1996).
13. R. Oliyai. Prodrugs of peptides and peptidomimetics for improved formulation and delivery. Adv. Drug Del. Rev. 19:275-286 (1996).
14. P. Artursson and J. Karlsson. Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells. Biochem. Biophys. Res. Commun. 175:880-885 (1991).
15. S. Yamashita, Y. Tanaka, Y. Endoh, Y. Taki, T. Sakane, T. Nadai, and H. Sezaki. Analysis of drug permeation across Caco-2 monolayer: implication for predicting in vivo drug absorption. Pharm. Res. 14:486-491 (1997).
16. P. Artursson. Epithelial transport of drugs in cell culture. I. A model for studying the passive diffusion of drugs over intestinal absorptive (Caco-2) cells. J. Pharm. Sci. 79:476-482 (1990).
17. K. S. Kim, R. V. Moquin, L. Qian, R. A. Morrison, S. M. Seiler, D. G. M. Roberts, M. L. Ogletree, S. Youssef, and S. Chong. Preparation of argatroban analog thrombin inhibitors with reduced basic guanidine moiety, and studies of their cell permeability and antithrombotic activities. Med. Chem. Res. 377-383 (1996).
18. B. J. Aungst and H. Saitoh. Intestinal absorption barriers and transport mechanisms, including secretory transport, for a cyclic peptide, fibrinogen antagonist. Pharm. Res. 13:114-119 (1996).
19. P. F. Augustijns, T. P. Bradshaw, L. S. Gan, R. W. Hendren, and D. R. Thakker. Evidence for a polarized efflux system in Caco-2 cells capable of modulating cyclosporin A transport. Biochem. Biophys. Res. Commun. 197:360-365 (1993).
20. K-I. Hosoya, K-J. Kim, and V. H. L. Lee. Age dependent expression of P-glycoprotein gp170 in Caco-2 cell monolayers. Pharm. Res. 13:885-890 (1996).
21. J. Hunter, B. H. Hirst, and N. L. Simmons. Drug absorption limited by P-glycoprotein-mediated secretory drug transport in human intestinal epithelial Caco-2 cell layers. Pharm. Res. 10:743-749 (1993).
22. J. Karlsson, S. M. Kou, J. Ziemniak, and P. Artursson. Transport of celiprolol across human intestinal epithelial (Caco-2) cells: mediation of secretion by multiple transporters including P-glycoprotein, Br. J. Pharmacol. 110:1009-1016 (1993).
23. P. S. Burton, R. A. Conradi, A. R. Hilgers, and N. F. Ho. Evidence for a polarized efflux system for peptides in the apical membrane of Caco-2 cells. Biochem. Biophys. Res. Commun. 190:760-766 (1993).
24. B. Sarkadi, M. Müller, Homolya, Z. Hollo, J. Seprodi, U. A. Germann, M. M. Gottesman, E. M. Price, and R. C. Boucher. Interaction of bioactive hydrophobic peptides with the human multidrug transporter. FASEB J. 8:766-770 (1994).
25. V. B. Lang. P. Langguth, C. Ottiger, H. Wunderli-Allenspach, D. Rognan, B. Rothen-Rutishauser, J. C. Perriard, S. Lang, J. Biber, and H. P. Merkle. Structure-permeation relations of met-enkephalin peptide analogues on absorption and secretion mechanisms in Caco-2 monolayers. J. Pharm. Sci. 86:846-853 (1997).
26. J. M. Ford and W. N. Hait. Pharmacology of drugs that alter multidrug resistance in cancer. Pharmacol. Rev. 42:155-199 (1990).
27. W. H. M. Peters, C. E. W. Boon, H. M. J. Roelofs, T. Wobbes, F. M. Nagengast, and P. G. Kremers. Expression of drug-metabolizing enzymes and P-170 glycoprotein in colorectal carcinoma and normal mucosa. Gastroenterology 103:448-455 (1992).
28. V. H. L. Lee and A. Yamamoto. Penetration and enzymatic barriers to peptide and protein absorption. Adv. Drug Del. Rev. 4:171-207 (1990).
29. J. P. Bai and G. L. Amidon. Structural specificity of mucosalcell transport and metabolism of peptide drugs: implication for oral peptide drug delivery. Pharm. Res. 8:969-978 (1992).
30. T. Weller, L. Alig, M. Beresini, B. Blackburn, S. Bunting, P. Hadváry, M. H. Müller, D. Knopp, B. Levet-Trafit, M. T. Lipari, N. B. Modi, M. Müller, C. J. Refino, M. Schmitt, P. Schönholzer, S. Weiss, and B. Steiner. Orally active fibrinogen receptor antagonists. 2. Amidoximes as prodrugs of amidines. J. Med. Chem. 39:3139-3147 (1996).
31. Z. Shahrokh, E. Lee, A. G. Olivero, R. A. Matamoros, K. D. Robarge, A. Lee, K. J. Weise, B. K. Blackburn, and M. F. Powell. Stability of alkoxycarbonylamidine predrugs. Pharm. Res. 15:434-441 (1998).