Calcitonin nasal absorption

Nasal absorption. Sucrose ester of coconut fatty acid in aqueous ethanol solution (sucrose cocoate SL-40) administered intrana-sally to anesthetized male Sprague-Dawley rats at a dose of 0.5% sucrose cocoate with insulin, produced a rapid and significant increase in plasma insulin level with a concomitant decrease in blood glucose levels. Administration of a dose of 0.5% sucrose cocoate with calcitonin produced a rapid increase in plasma calcitonin levels and a concomitant decrease in plasma calcium levels . 

Shin, B.S., et al. 2004. Nasal absorption and pharmacokinetic disposition of salmon calcitonin modified with low molecular weight polyethylene glycol. Chem Pharm Bull 52 957. 

Morimoto, K., Morisaka, K., and Kamada, A. (1985), Enhancement of nasal absorption of insulin and calcitonin using polyacrylic acid gel,/. Pharm. Pharmacol., 37,134-136. 

Finally, it should be noted that during the last decade both weakly crosslinked poly(acrylic acid) derivatives and chitosan derivatives were described as safe penetration enhancers for hydrophilic compounds especially as they can trigger mechanisms of tight junction opening of mucosal tissues and did not show acute toxicity. Poly(acrylic acid) derivatives were shown to have excellent mucoadhesive properties and can inhibit the activity of gut enzymes, such as trypsin, chymo-trypsin, and carboxypepsidases. Chitosan salts and Ni-trimethylchitosan chloride revealed to be potential absorption enhancers for nasal absorption of calcitonin and insulin and for the intestinal absorption of buserilin.f ... 

Classical enzyme inhibitors such as bacitracin, bes-tatin, and amastatin have been found to be effective for improving the nasal absorption of various peptide drugs such as LHRH and calcitonin. These inhibitors having peptide like structures appear to exert their inhibitory effects by a competitive mechanism. In addition, camostat mesilate and nafamostat mesilate, which are clinically used as primary ingredients for pancreatic diseases, have been found to improve the nasal absorption of vasopressin, desmopressin, and calcitonin by inhibiting aminopeptidase and trypsin activity. 

Sinswat, P. Tengamnuay, P. Enhancing effect of chitosan on nasal absorption of salmon calcitonin in rats comparison with hydroxypropyl- and dimethyl-beta-cyclodextrins. Int. J. Pharm. 2003, 257 (1-2), 15-22. 

Tengamnuay, S. R, Mitra, A. K. (1997]. Chitosans as nasal absorption enhancers of salmon calcitonin Comparison with hydroiqrpropyl-and dimethyl-b-cyclodextrins, Pharm. Res., 14, SI 29. 

Calcitonin (Miacalcin, Miacalcin Nasal Spray) is a synthetic 32-amino acid polypeptide that is identical to salmon calcitonin. Salmon calcitonin is more potent than human calcitonin because of its higher affinity for the human calcitonin receptor and its slower metabolic clearance. Administration is by subcutaneous or intramuscular injection or by nasal spray. The absorption of the nasal form is slower than that of the parenteral routes. 

Calcitonin is a peptide hormone produced in the thyroid gland that serves to lower serum calcium and phosphate levels by inhibiting bone resorption. Calcitonin has been used in the treatment of a variety of diseases, such as primary hyperparathyroidism, Paget s disease, and postmenopausal osteoporosis [99,100]. Salmon calcitonin has a longer half-life than human calcitonin. Salmon calcitonin, 3.6 kDa, is available as a nasal formulation that contains only benzalkonium chloride as a preservative, without an absorption enhancer, and as a parenteral product for injection. The direct effect of benzalkonium chloride on the nasal mucosa is under... 

The nasal application of drugs is an area of growing interest (21) and a number of publications has shown that simple molecules as well as more complex species (eg calcitonin, insulin etc) can be well absorbed by this route, either directly or in the presence of so-called absorption enhancers. One problem with such materials could be too rapid clearance of the delivery system from the nasal cavity through the efficient action of the mucociliary system. For this reason Ilium has considered the use of microsphere systems. 

Polyacrylic acid aqueous gel enhances the absorption of calcitonin after nasal as well as rectal administration. When [Asul,7]-eel calcitonin (lOU/kg) was administered nasally in polyacrylic acid gel at a concentration of 0.1% w/v, a prominent hypocalcemic effect was seen in the first 30min. Nasal administration of [Asul,7]-eel calcitonin in saline had no hypocalcemic effect at the same dose when given by the nasal route. In addition to this, the effect of [Asul,7]-eel calcitonin in the dose range of 1-10 U/kg has also been studied. The resulting data showed that a rapid reduction in plasma calcium concentrations can be achieved at doses of 5 and 10 U/kg however, at doses of 1 U/kg only a small reduction in the plasma calcium concentration was observed, suggesting that polyacrylic acid gel can be used for the intranasal administration of peptides such as calcitonin. The possible side effects, however, were not known at the time the study was performed [76-78],... 

There is particular interest in the nasal mucosa because it can provide systemic absorption of dmgs that otherwise must be administered by injection. These are often polypeptide dmgs. Calcitonin and vasopressin-like dmgs (nonapeptides) for diabetes insipidus in patients with panhypopituitarism are examples. 

Successful nasal delivery of peptide compounds has led to a number of peptide drugs being marketed for systematic absorption. These peptide drugs include buserelin (Supre-fact , Hoechst), gonadorelin (Kryptocur , Hoechst), protirelin (Relefact TRH nasal, Hoechst), calcitonin (Miacalcic , Sandoz), nafarelin (Synarel , Syntex) and desmopressin (Minirin , Ferring). Table 13.5 summarises the characteristics of some peptides studied in the nose. 

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