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Rectal Absorption Enhancement of Des-Enkephalin-γ-Endorphin (DEγE) by Medium-Chain Glycerides and EDTA in Conscious Rats

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Abstract

The stability of the neuroleptic peptide des-enkephalin-γ-endorphin (DEγE; Org 5878) in the rectal lumen and the rectal bioavailability of DEγE were investigated in conscious rats. Furthermore, the influence of peptidase inhibition, peptidase saturation, and absorption enhancement on DEγE bio-availability were evaluated. Na2EDTA (0.25%, w/v) prolonged the degradation half-life of DEγE in the ligated colon from 33 ± 7 to 93 ± 45 min. Without adjuvant, tritium-labeled DEγE was absorbed from the rat rectum to a very low extent (0–4%). After administration of an excess of unlabeled DEγE or with Na2EDTA, comparable results were obtained. The medium-chain glyceride preparation MGK markedly enhanced the rectal DEγE bioavailability, up to 8–20%, which was further increased to 10–44% by coadministration of Na2EDTA. No substantial influence of varying the rectal delivery rate was observed. The results suggest that absorption enhancement and enzyme inhibition both are essential for effective increase of rectal peptide bioavailability.

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REFERENCES

  1. J. W. van Nispen and H. M. Greven. Pharm. Ther. 16:67–102 (1982).

    Google Scholar 

  2. D. de Wied. In E. R. de Kloet, V. M. Wiegant, and D. de Wied (eds.), Neuropeptides and Brain Function, Progr. Brain Res., Vol. 72, Elsevier, Amsterdam, 1987, pp. 93–108.

    Google Scholar 

  3. S. A. Adibi and Y. S. Kim. In L. R. Johnson (ed.), Physiology of the Gastrointestinal Tract, Raven Press, New York, 1981, pp. 1073–1095.

    Google Scholar 

  4. V. H. L. Lee. Pharm. Int. 7:208–212 (1986).

    Google Scholar 

  5. P. Gruber, M. A. Longer, and J. R. Robinson. Adv. Drug Del. Rev. 1:1–18 (1987).

    Google Scholar 

  6. M. J. Humphrey. In S. S. Davis, L. Illum, and E. Tomlinson (eds.), Delivery Systems for Peptide Drugs, Plenum Press, New York, 1986, pp. 139–151.

    Google Scholar 

  7. A. G. de Boer, F. Moolenaar, L. G. J. de Leede, and D. D. Breimer. Clin. Pharmacokin. 7:285–311 (1982).

    Google Scholar 

  8. L. G. J. de Leede, A. G. de Boer, C. P. J. M. Roozen, and D. D. Breimer. J. Pharmacol. Exp. Ther. 225:181–185 (1983).

    Google Scholar 

  9. A. K. Mitra. Pharm. Int. 323–324 (1986).

  10. H. M. Jennewein, F. Waldeck, and W. Konz. Drug Res. 24:1225–1228 (1974).

    Google Scholar 

  11. M. Hirata, S. Futaguchi, T. Tamura, K. Odaguchi, and A. Tanaka. Chem. Pharm. Bull. 26:1061–1065 (1978).

    Google Scholar 

  12. M. Saito, T. Kumasaki, Y. Yaoi, N. Nishi, A. Arimura, D. H. Coy, and A. V. Schally. Fertil. Steril. 28:240–245 (1977).

    Google Scholar 

  13. T. Mitsuma and T. Nogimori. Acta Endocrinol. 107:207–212 (1984).

    Google Scholar 

  14. W. A. Ritschel and G. B. Ritschel. Meth. Find. Exp. Clin. Pharmacol. 6:513–529 (1984).

    Google Scholar 

  15. V. Bocci, F. Corradeschi, A. Naldini, and E. Lencioni. Int. J. Pharm. 34:111–114 (1986).

    Google Scholar 

  16. I. Yamazaki. In F. Labrie, A. Belanger, and A. Dupont (eds.), LHRH and Its Analogues, Elsevier, Amsterdam, 1984, pp. 77–91.

    Google Scholar 

  17. J. A. Moore, S. A. Pletcher, and M. J. Ross. Int. J. Pharm. 34:35–43 (1986).

    Google Scholar 

  18. K. Morimoto, H. Akatsuchi, R. Aikawa, M. Morishita, and K. Morisaka. J. Pharm. Sci. 73:1366–1368 (1984).

    Google Scholar 

  19. T. Yagi, N. Hakui, Y. Yamasaki, R. Kawamori, M. Shichiri, H. Abe, S. Kim, M. Miyake, K. Kamikawa, T. Nishihata, and A. Kamada. J. Pharm. Pharmacol. 35:177–178 (1983).

    Google Scholar 

  20. M. Sekine, K. Sasahara, R. Okada, and S. Awazu. J. Pharmacobio-Dyn. 8:645–652 (1985).

    Google Scholar 

  21. Y. P. Loh. Am. Rev. Neurosci. 7:189–222 (1984).

    Google Scholar 

  22. M. Sekine, K. Sasahara, T. Kojima, K. Hasegawa, R. Okada, and S. Awazu. J. Pharmacobio-Dyn. 7:856–863 (1984).

    Google Scholar 

  23. J. Nakamura, K. Shima, T. Kimura, S. Muranishi, and H. Sezaki. Chem. Pharm. Bull. 26:857–863 (1978).

    Google Scholar 

  24. E. J. van Hoogdalem, H. J. M. van Kan, A. G. de Boer, and D. D. Breimer. J. Controlled Release 7:53–60 (1988).

    Google Scholar 

  25. J. C. Verhoef and H. M. van den Wildenberg. Regul. Peptides 14:113–124 (1986).

    Google Scholar 

  26. J. C. Verhoef, H. M. van den Wildenberg, and J. W. van Nispen. Eur. J. Drug Metab. Pharmacokin. 11:291–302 (1986).

    Google Scholar 

  27. W. L. Chiou. J. Pharmacokin. Biopharm. 6:539–546 (1978).

    Google Scholar 

  28. E. J. van Hoogdalem, A. M. Stijnen, A. G. de Boer, and D. D. Breimer. J. Pharm. Pharmacol. 40:329–332 (1988).

    Google Scholar 

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Authors and Affiliations

  1. Center for Bio-Pharmaceutical Sciences, Division of Pharmacology, Sylvius Laboratories, Leiden University, P.O. Box 9503, 2300, RA Leiden, The Netherlands

    Ewoud J. van Hoogdalem, Cornelia D. Heijligers-Feijen, Albertus G. de Boer & J. Coos Verhoef

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  1. Ewoud J. van Hoogdalem
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  2. Cornelia D. Heijligers-Feijen
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  3. Albertus G. de Boer
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  4. J. Coos Verhoef
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  5. Douwe D. Breimer
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van Hoogdalem, E.J., Heijligers-Feijen, C.D., de Boer, A.G. et al. Rectal Absorption Enhancement of Des-Enkephalin-γ-Endorphin (DEγE) by Medium-Chain Glycerides and EDTA in Conscious Rats. Pharm Res 6, 91–95 (1989). https://doi.org/10.1023/A:1015864022305

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