Abstract
The effect of the polypeptide salmon calcitonin (sCT) on serum calcium concentrations following intranasal and intravenous administration was studied in young rabbits. A small, hypocalcemic effect was observed after nasal administration of sCT without additives, indicating that the nasal sCT absorption was low. The absorption could be improved by addition of an absorption-enhancing adjuvant to the nasal preparation. The absorption, however, was still far from complete as was apparent from the much stronger effect of intravenously injected sCT. When a number of sCT doses were given during a 10-week period, the hypocalcemic effect per sCT dose in the young rabbits decreased after intravenous and, although less pronounced, after nasal administration. The decreased response to sCT is probably not related to the induction of neutralizing antibodies or desensitization of sCT receptors, but is more likely associated with the age-dependent level of bone activity.
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References
Reginster JY, Alber A, Lecart MP, Lambelin P, Denis P, Deroisy R, Fontaine MA, Franchimont P (1987) 1-Year controlled randomised trial of prevention of early post-menopausal bone loss by intranasal calcitonin. Lancet 1481–1483
Nagant de Deuxchaisnes C, Devogelaer JP, Haux JP, Dufour JP, Esselinckx W, Engelbeen JP, Stasse P, Hermans P, De Buisseret JP (1987) New modes of administration of salmon calcitonin in Paget's disease. Clin Orthop 217:56–71
Azria M (1989) The calcitonins: physiology and pharmacology. Karger, Basel
Singer FR, Fredericks RS, Minkin C (1980) Salmon calcitonin therapy for Paget's disease of bone, the problem of acquired clinical resistance. Arthritis Rheum 23:1148–1153
Levy F, Muff R, Dotti-Sigrist S, Dambacher MA, Fisher JA (1988) Formation of neutralizing antibodies during intranasal synthetic salmon calcitonin treatment of Paget's disease. J Clin Endocrinol Metab 67:541–545
Bouizar Z, Rostène WH, Milhaud G (1987) Down-regulation of rat kidney calcitonin receptors by salmon calcitonin infusion evidenced by autoradiography. Proc Natl Acad Sci 84:5125–5128
Tashjihan AH JR, Wright DR, Ivey JL, Pont A (1978) Rec Prog Horm Res 34:285–332
Overgaard K, Agnusdei D, Hansen MA, Maioli E, Christiansen C, Gennari C (1991) Dose response bioactivity and bioavailability of salmon calcitonin in premenopausal and postmenopausal women. J Clin Endocrinol Metab 72:344–349
Hanson M, Gazdick G, Cahill J, Augustine M (1986) Intranasal delivery of the peptide salmon calcitonin. In: Davis SS, Illum L, Tomlinson E (eds) Delivery systems for peptide drugs. Plenum Press, New York, pp 233–242
Pontiroli AE, Alberetto M, Calderara A, Pajetta E, Pozza G (1989) Nasal administration of glucagon and human calcitonin to healthy subjects: a comparison of powders and spray solutions and differing enhancing agents. Eur J Clin Pharmacol 37:427–430
Vee VHL, Yamamoto A, Bhaskar Kompella U (1991) Mucosal penetration enhancers for facilitation of peptide and protein drug absorption. Crit Rev Ther Drug Carrier Syst 8:91–192
Van Bree JBMM, De Boer AG, Danhof M, Verhoef J, Van Wimersma Greidanus TjB Breimer DD (1988) Radioimmunoassay of desglycinamide arginine vasopressin and its application in a pharmacokinetic study in the rat. Peptides 9:555–559
Engvall E (1980) Enzyme immunoassay: ELISA and EMIT. In: Longone JJ (ed) Methods in enzymology, vol. 70. Academic Press, New York, pp 419–439
Hirai S, Yashiki T, Mima H (1981) Effect of surfactants on the nasal absorption of insulin in rats. Int J Pharm 9:165–172
Morimoto K, Miyazaki M, Yamaguchi H, Kakemi M (1992) Effects of proteolytic enzyme inhibitors on the nasal absorption of vasopressin, an analogue and calcitonin. Proc Int Symp Control Rel Bioact Mater 19:218–219
Reginster JY, Azria M, Gaspar S, Bleicher M, Franchimont N, Behhar M, Albert A, Franchimont P (1992) Endogenous production of specific antibodies does not decrease hypocalcemic response of calcitonin in young rabbits. Calcif Tissue Int 50: 518–520
Singer FR, Woodhouse NJY, Parkinson DK, Joplin GF (1969) Some acute effects of administered porcine calcitonin in man. Clin Sci 37:181–190
Azria M, Kiger JL (1974) Nouvelle technique de dosage biologique de la calcitonine par utilisation du porc miniature. Thérapie 29:753–766
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Schipper, N.G.M., Romeijn, S.G., Verhoef, J. et al. Hypocalcemic effect of salmon calcitonin following single and repeated nasal and intravenous administration in young rabbits. Calcif Tissue Int 54, 50–55 (1994). https://doi.org/10.1007/BF00316290
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DOI: https://doi.org/10.1007/BF00316290