Nasal Absorption of Enkephalins in Rats

  • Kenneth S. E. Su
  • Kristina M. Campanale
  • Laurane G. Mendelsohn
  • Gail A. Kerchner
  • Christian L. Gries
Part of the NATO ASI Series book series (NSSA, volume 125)

Abstract

In recent years, the possibility that the intranasal administration route might be useful for many compounds which are not absorbed orally has received a great deal of attention. For instance, the β-blocker propranolol (Hussain et al, 1979, 1980 a, b), the contraceptive agent progesterone (David et al, 1981; Hussain et al, 1981) and the anti-arrhythmic compound clofilium tosylate (Su et al, 1984) have been shown to be effectively absorbed via the intranasal route when compared to oral administration. These compounds undergo extensive degradation due to first-pass hepatic metabolism which can be minimized after nasal administration. For drugs which are poorly absorbed by the oral route such as sulbenicillin, cefazolin, and cephacetrile, it was demonstrated that the percent dose excreted in urine after nasal administration was nearly one-half of that after intramuscular administration (Hirai et al, 1981). The absorption of low molecular weight polypeptides, luteinising hormone-releasing hormone (LH-RH) and its analogues used as a contraceptive agent, was evaluated by the nasal route (Fink et al, 1974; Berquist et al, 1979; Gennser and Liedholm, 1974; London et al, 1973; Anik et al, 1984). Although the absorption efficiency by the nasal route was lower than the I.V. route for these polypeptides, the absorption was reproducible, and the advantage of non-parenteral route for such a compound was an important factor. Research has also been carried out on the nasal absorption of high molecular weight polypeptides such as insulin (Moses et al, 1983; Hirai et al, 1978, 1981 a,b), interferon (Greenberg et al, 1978; Harmon et al, 1976; 1977; Johnson et al, 1976) and growth hormone releasing factor (Evans et al, 1983).

Keywords

Nasal Mucosa Intranasal Administration Tritiated Water Nasal Administration Nasal Route 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Anik, S. T., McRae, G., Nerenberg, C., Worden, A., Foreman, J., Hwang, J. Y., Kushinsky, S., Jones, R. E., and Vickery, B., 1984, J. Pharm. Sci., 73:684.PubMedCrossRefGoogle Scholar
  2. Berquist, C., Nillius, S. J., and Wide, L., 1979, Lancet, 2:215.CrossRefGoogle Scholar
  3. David, G. F. X., Puri, C. P., and Anand Kuman, T. C, 1981, Experimentia, 37: 533.CrossRefGoogle Scholar
  4. Evans, W. W., Borges, J. L. C., Kaiser, D. L., Vance, M. L., Sellers, R. P., MacLeod, R. M., Vale, W., Rivier, J., and Thorner, M. O., 1983, J. Clin. Endocr. Metab., 57:1081.PubMedCrossRefGoogle Scholar
  5. Fink, G., Gennser, G., Liedholm, P., Thorell, J., and Mulder, J., 1974, J. Endocr., 63:351.PubMedCrossRefGoogle Scholar
  6. R. C. A. Frederickson, Life Sci., 21, 23 (1970).Google Scholar
  7. Gennser, G., and Liedholm, P., 1974, Lancet, 1:865.PubMedCrossRefGoogle Scholar
  8. Gesellchen, P. D., Tafur, S., and Shields, J. E., 1979, “Peptides: Structure and Biological Function, Proc. of the Sixth American Peptide Symp.”, E. Gross and J. Neienhofer, Eds., Pierce Chemical Co., Rockfold, I11., pp. 117–120.Google Scholar
  9. Gesellchen, P. D., Parli, C. J., and Frederickson, R. C. A., 1980, “Peptides: Synthesis-Structure-Function, Proc. of the Seventh Ameri. Peptide Symp.”, D. H. Rich and E. Gross, Eds., Pierce Chem. Co., Rockfold, I11., pp. 637–640.Google Scholar
  10. Greenberg, S. B., Harmon, M. W., Johnson, P. E., and Couch, R. B., 1978, Antimicro. Agents and Chemot., 14: 596.CrossRefGoogle Scholar
  11. Harmon, M. W., Greenberg, S. B., and Couch, R. B., 1976, Proc. Soc. Exp. Biol. Med., 152:598.PubMedGoogle Scholar
  12. Harmon, M. W., Greenberg, S. R., Johnson, P. E., and Couch, R. B., 1977, Infect. Immun., 16:480.PubMedGoogle Scholar
  13. Hirai, S., Yashiki, T., Matsuzawa, T., and Mima, H., 1981, Int. J. Pharm., 7:317.CrossRefGoogle Scholar
  14. Hirai, S., Ikenaga, T., and Matsuzawa, T., 1978, Int. J. Pharm., 27:296.Google Scholar
  15. Hirai, S., Yashiki, T., and Mima, H., 1981a, Int. J. Pharm., 9:165.CrossRefGoogle Scholar
  16. Hirai, S., Yashiki, T., and Mima, H., 1981b, Int. J. Pharm., 9:173.CrossRefGoogle Scholar
  17. Hussein, A., Hirai, S., and Bawarshi, R., 1979, J. Pharm. Sci., 68:1196.CrossRefGoogle Scholar
  18. Hussain, A., Foster, T., Hirai, S., Kashihara, T., Batenhorst, R., and Jones, M., 1980a, J. Pharm. Sci., 69:1240.PubMedCrossRefGoogle Scholar
  19. Hussain, A., Hirai, S., and Bawarshi, R., 1980b, J. Pharm. Sci., 69:1411.PubMedCrossRefGoogle Scholar
  20. Hussain, A., Hirai, S., and Bawarshi, R., 1981, J. Pharm. Sci., 70:466.PubMedCrossRefGoogle Scholar
  21. Johnson, P. E., Greenberg, S. B., Harmon, M. W., Alford, B. R., and Couch, R. B., 1976, J. Clin. Microbiol., 4:106.PubMedGoogle Scholar
  22. Leander J. D., and Wood, C. R., Peptides, 3:771.Google Scholar
  23. London, D. R., Butt, W. R., Lynch, S. S., Marshell, J. C. Owusu, S., Robinson, W. R., and Stephenson, J. M., 1973, J. Clin. Endocrinol. Metab., 37:829.PubMedCrossRefGoogle Scholar
  24. Moses, A. C., Gordon, G. S., Carey, M. C., and Flier, J. S., 1983, Diabetes, 32:1040.PubMedCrossRefGoogle Scholar
  25. Motta, M., 1980, “The Endocrine Functions of the Brain”, Chap 12, pp. 233–270, Raven Press, New York, N.Y.Google Scholar
  26. aai]Proctor D. F., and Andersen, I. B., 1982, “The Nose: Upper Airway Physiology and the Atmospheric Environment”, Chap. 2 and 3, pp. 23–69, Elsevier Biomedical Press, Amsterdam, Netherlands.Google Scholar
  27. Su, K. S. E., Campanale, K. M., and Gries, C. L., 1984, The Nose: Upper Airway Physiology and the Atmospheric Environment, 73:1251.Google Scholar

Copyright information

© Springer Science+Business Media New York 1986

Authors and Affiliations

  • Kenneth S. E. Su
    • 1
  • Kristina M. Campanale
    • 1
  • Laurane G. Mendelsohn
    • 1
  • Gail A. Kerchner
    • 1
  • Christian L. Gries
    • 1
  1. 1.Pharmaceutical Research Department, Division of CNS and Endocrine Research, and Toxicology DivisionLilly Research Laboratories, Eli Lilly and CompanyIndianapolisUSA

Personalised recommendations