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Delivery systems for LHRH and analogs

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LHRH and Its Analogs

Part of the book series: Advances in Reproductive Health Care ((ARHE,volume 1))

Abstract

The delivery of polypeptide and protein drugs by a convenient and effective method is a major challenge in the development of these compounds as therapeutic agents. Due to degradation and/or lack of absorption in the gastrointestinal tract, large, uneconomical doses are required for activity following oral administration. Rectal, nasal and depot injectable preparations have been investigated for the delivery of insulin but success has been limited. The injectable route, which assures availability of drug to the patient, is still the most frequently used. Efficient absorption and low variability of absorption are among the criteria to be emphasized when developing alternative delivery systems.

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References

  • Anderson, J. M., Gibbons, D. F., Martin, R. L., Hiltner, A. and Woods, R. (1974). The potential for poly-α-amino acids as biomaterials. J. Biomed. Mater. Res. Symp., 5, 197

    Article  Google Scholar 

  • Anderson, L. C., Wise, D. L. and Howes, J. F. (1976). An injectable sustained release fertility control system. Contraception, 13, 375

    Article  PubMed  CAS  Google Scholar 

  • Anik, S. T., McRae, G., Nerenberg, C., Worden, A., Foreman, J., Hwang, J. Y., Kuskinsky, S., Jones, R. E. and Vickery, B. (1984). Nasal absorption of nafarelin acetate or [d-Nal(2)6]LHRH a decapeptide, in rhesus monkeys, J. Pharm. Sci., (In press)

    Google Scholar 

  • Barron, J. L., Millar, R. P. and Searle, D. (1982). Metabolic clearance and plasma halfdisappearance time of d-Trp6 and exogenous luteinizing hormone-releasing hormone. J. Clin. Endocrinol. Metab., 54, 1169

    Article  PubMed  CAS  Google Scholar 

  • Beck, L. R., Cowsar, D. L., Lewis, D. H., Gibson, J. W. and Flowers, C. E. (1979). New long-acting injectable microcapsule contraceptive system. Am. J. Obstet. Gynecol., 135, 419

    PubMed  CAS  Google Scholar 

  • Beck, L. R., Ramos, R. A., Flowers, C. E., Lopez, G. Z., Lewis, D. H. and Cowsar, D. R. (1981). Clinical evaluation of injectable biodegradable contraceptive system. Am. J. Obstet. Gynecol., 140, 799

    PubMed  CAS  Google Scholar 

  • Bergquist, C., Nillius, S. J. and Wide, L. (1982). Long-term intranasal luteinising hormone-releasing hormone agonist treatment for contraception in women. Fertil. Steril., 38, 190

    PubMed  CAS  Google Scholar 

  • Corbin, A. and Bex, F. J. (1982). Physiology and contraceptive effects of LHRH and agonistic analogs in female animals. In Zatuchni, G. I., Shelton, J. D. and Sciarra, J. J. (eds.) LHRH Peptides as Female and Male Contraceptives, pp. 68–84. (Philadelphia: Harper and Row)

    Google Scholar 

  • Dahlen, H. G., Keller, E. and Schneider, H. P. G. (1974). Linear dose dependent LH release following intranasally sprayed LRH. Horm. Metab. Res., 6, 510

    Article  PubMed  CAS  Google Scholar 

  • Fink, G., Gennser, G., Liedholm, P., Thorell, J. and Malder, J. (1974). Comparison of plasma levels of luteinizing hormone-releasing hormone in men after intravenous or intranasal administration. J. Endocrinol., 63, 351

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez-Barcena, D., Miller M. C. III, Coy, D. H., Kastin, A. J., Schalch, D. S., Schally, A. V. and Escalante-Herrera, A. (1975). Stimulation of luteinizing hormone (LH) release after oral administration of an analogue of LH releasing hormone. Lancet, 6 December 1126

    Google Scholar 

  • Gonzalez-Barcena, D., Kastin, J. A., Schalch, D. S., Coy, D. H. and Schally, A. V. (1976). Prolonged elevation of luteinizing hormone (LH) after intranasal administration of an analog of LH-releasing hormone. Fertil. Steril., 27, 1246

    PubMed  CAS  Google Scholar 

  • Happ, J., Hartmann, U., Weber, T., Cordes, U. and Beyer, J. (1978). Gonadotropin and testosterone secretion in normal human males after stimulation with gonadotropin-releasing hormone (GnRH) or potent GnRH analogs using different modes of application. Fertil. Steril., 30, 666

    PubMed  CAS  Google Scholar 

  • Harrigan, S. E., McCarthy, D. A., Reuning, R. and Thies, C. (1978). Release of naltrexone pamoate from injectable microcapsules. Midl. Macromol. Monogr., 5, 91

    CAS  Google Scholar 

  • Haug, E., and Torjesen, P. (1973). Effect of synthetic luteinizing hormone and follicle stimulating hormone-releasing hormone (LH/FSH-RH) on serum levels of LH, FSH, thyrotropin (TSH) and growth hormone (HGH) in normal male subjects. Acta Endocrinol., 73, 465

    PubMed  CAS  Google Scholar 

  • Heller, J. (1980). Controlled release of biologically active compounds from bioerodible polymers. Biomaterials, 1, 51

    Article  PubMed  CAS  Google Scholar 

  • Heller, J., Baker, R. W., Gale, R. M. and Rodin, J. D. (1978). Controlled drug release by polymer dissolution. I. Partial esters of maleic anhydride copolymers - properties and theory. J. Appl. Polym. Sci., 22, 1991

    Article  CAS  Google Scholar 

  • Heller, J., Penhale, D. W. H., Helwing, R. F. and Fritzinger, B. K. (1982). Controlled release of norethindrone from poly (ortho ester). In Roseman, T. J. and Mansdorf, S. Z. (eds.) Controlled Released Delivery Systems (New York: Dekker)

    Google Scholar 

  • Hirai, S., Yashiki, T. and Mima, H. (1981). Mechanisms for the enhancement of the nasal absorption of insulin by surfactants. Int. J. Pharm., 9, 173

    Article  CAS  Google Scholar 

  • Hussain, A., Foster, T., Hirai, S., Kashihara, T., Batenhorst, R. and Jones, M. (1980). Nasal absorption of propranolol in humans. J. Pharm. Sci., 69, 1240

    Article  PubMed  CAS  Google Scholar 

  • Kent, J. S., Sanders, L. M., McRae, G. I., Vickery, B. H., Tice, T. R. and Lewis, D. H. (1982). In vivo controlled release of an LHRH analog from injected polymeric microcapsules. Contracept. Deliv. Syst., 3, 58

    Google Scholar 

  • London, D. R., Butt, W. R., Lynch, S. S., Marshall, J. C., Owusu, S., Robinson, W. R. and Stephenson, J. M. (1973). Hormonal responses for intranasal luteinizing hormone-releasing hormone. J. Clin. Endocrinol. Metab., 37, 829

    Article  PubMed  CAS  Google Scholar 

  • Marshall, J. C., Anderson, D. C., Fraser, T. R. and Hasoulis, P. (1973). Human luteinizing hormone in man: Studies of metabolism and biological action. J. Endocrinol., 56, 431

    Article  PubMed  CAS  Google Scholar 

  • Miyachi, Y., Meckleburg, R. S., Hansen, J. W. and Lipsett, M. B. (1973). Metabolism of 125I-Luteinizing Hormone-Releasing Hormone. J. Clin. Endocrinol. Metab., 37, 63

    Article  PubMed  CAS  Google Scholar 

  • Mortimer, C. H., Besser, G. M., Hook, J. and McNeilly, A. S. (1974). Intravenous, intramuscular, subcutaneous and intranasal administration of LH/FSH-RH: The duration of effect and occurrence of asynchronous pulsatile release of LH and FSH. Clin. Endocrinol., 3, 19

    Article  CAS  Google Scholar 

  • Nerenberg, C., Foreman, J. and Kushinsky, S. (1983). Radioimmunoassay for (d-naphthyl alanine(2)6)LHRH (RS-94991) in plasma or serum. Abstr. Ann. Mtg. Endocr. Soc., 1983, San Antonio, Texas

    Google Scholar 

  • Nestor, J. J. Jr., Ho, T. L., Simpson, R. A., Horner, B. L., Jones, G. H., McRae, G. I. and Vickery, B. H. (1982). The synthesis and biological activity of some very hydrophobic analogs of luteinizing hormone-releasing hormone. J. Med. Chem., 25, 795

    Article  PubMed  CAS  Google Scholar 

  • Okada, H., Yamazaki, I., Ogawa, Y., Hirai, S., Yashiki, T. and Mima, H. (1982). Vaginal absorption of a potent luteinizing hormone-releasing hormone analog (Leuprolide) in rats I: Absorption by various routes and absorption enhancement. J. Pharm. Sci., 71, 1367

    Article  PubMed  CAS  Google Scholar 

  • Okada, H., Yamazaki, I., Yashiki, T. and Mima, H. (1983). Vaginal absorption of a potent luteinizing hormone-releasing hormone analogue (Leuprolide) in rats II: Mechanism of absorption enhancement with organic acids. J. Pharm. Sci., 72, 75

    Article  PubMed  CAS  Google Scholar 

  • Pitt, C. G., Marks, T. A. and Schindler, A. (1980). Biodegradable drug delivery systems based on aliphatic polyesters: application to contraceptives and narcotic antagonists. In Lewis, D. (ed.) Controlled Release of Bioactive Materials, pp. 19–43. (London: Academic Press)

    Google Scholar 

  • Rebar, R., Yen, S. S. C., Vandenberg, G., Naftolin, F., Ehara, Y., Engblom, S., Ryan, K. J., Rivier, J., Amoss, M. and Guillemin, R. (1972). Gonadotropin responses to synthetic LRF: Dose response relationship in men. J. Clin. Endocrinol. Metab., 36, 10

    Article  Google Scholar 

  • Reel, J. R., Humphrey, R. R., Vaitkus, J. W. and Dermody, W. C. (1975). Stimulation of LH release and ovulation in the rat by cutaneous application of luteinizing hormone-releasing hormone (LH-RH) in dimethyl sulfoxide (DMSO). Endocr. Res. Commun., 2, 327

    Article  PubMed  CAS  Google Scholar 

  • Saito, M., Kumasaki, T., Yaoi, Y., Nishi, N., Arimura, A., Coy, D. and Schally, A. V. (1977). Stimulation of luteinizing hormone (LH) and follicle-stimulating hormone by [d-Leu6, des-Gly10-NH2] LH-releasing hormone ethylamide after subcutaneous, intravaginal, and intrarectal administration to women. Fertil. Steril., 28, 240

    PubMed  CAS  Google Scholar 

  • Sanders, L., Kent, J., McRae, G., Vickery, B., Tice, T. and Lewis, D. (1982). Controlled release of a GnRH analogue from injected polymeric microcapsules: formulation characteristics. Arch. Androl., 9, 91

    Google Scholar 

  • Seyler, L. E. Jr., (1975). Disappearance of biologic activity of synthetic LRH in normal and hypogonadal men. J. Clin. Endocrinol. Mètab., 41, 1155

    Article  PubMed  CAS  Google Scholar 

  • Sidman, K. R., Schwope, A. D., Steber, W. D., Rudolph, S. E. and Pontin, S. B. (1980). Biodegradable, implantable sustained release systems based on glutamic acid copolymers. J. Memb. Sci., 7, 277

    Article  CAS  Google Scholar 

  • Thies, C. (1976). Development of injectable microcapsules for use in the treatment of narcotic addiction. In Willette, R. E., (ed.) Research Monograph Series, 4, pp. 19–20

    Google Scholar 

  • Thies, C. (1981). Biodegradable polymers for parenteral administration. Int. J. Pharm. Tech. Prod. Mfr., 2, 25

    CAS  Google Scholar 

  • Turner, D., Turner, E. A., Aparicio, N. J., Schwarzstein, L., Coy, D. H. and Schally, A. V. (1976). Response of luteinizing hormone and follicle-stimulating hormone to different doses of d-Leucine-6-LH-RH Ethylamide in oligospermic patients. Fertil. Steril., 27, 545

    PubMed  CAS  Google Scholar 

  • Wise, D. L., McCormick, G. J., Willet, G. P., Anderson, L. C. and Howes, J. F. (1978). Sustained release of sulphadiazine. J. Pharm. Pharmacol., 30, 686

    Article  PubMed  CAS  Google Scholar 

  • Yolles, S. and Morton, D. F. (1978). Timed-release depot for anti-cancer agents II. Acta Pharm. Suec., 15, 382

    PubMed  CAS  Google Scholar 

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Authors

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B. H. Vickery J. J. Nestor Jr. E. S. E. Hafez

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© 1984 MTP Press Limited

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Anik, S.T., Sanders, L.M., Chaplin, M.D., Kushinsky, S., Nerenberg, C. (1984). Delivery systems for LHRH and analogs. In: Vickery, B.H., Nestor, J.J., Hafez, E.S.E. (eds) LHRH and Its Analogs. Advances in Reproductive Health Care, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-5588-2_33

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  • DOI: https://doi.org/10.1007/978-94-009-5588-2_33

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-8963-0

  • Online ISBN: 978-94-009-5588-2

  • eBook Packages: Springer Book Archive

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