Pharmacological Actions All calcitonins have a similar structure, a single chain of 32 amino acids. The order of the seven amino acids arranged in a loop at the N-terminus varies from species to species. Salmon calcitonin is more effective and has a longer duration of action than mammalian calcitonin because of its high affinity for the receptor binding site. Salmon calcitonin inhibits osteoclast activity through its specific receptor. It significantly reduces bone turnover to normal levels in cases of increased bone resorption, such as osteoporosis. Salmon calcitonin has been shown to have analgesic effects in animal models and humans, possibly as a result of direct action on the central nervous system. It produces significant clinical biological effects in humans when administered in a single dose. Urinary excretion of calcium, phosphorus, and sodium (by reducing tubular reabsorption) is increased and urinary hydroxyproline excretion is significantly decreased after administration. Prolonged parenteral administration of the drug resulted in a significant decrease in bone turnover markers such as collagen pyridine cross-linking and bone alkaline phosphatase isoenzymes. Calcitonin inhibits gastric and pancreatic secretion. Due to these properties, this product is beneficial in the treatment of acute pancreatitis. Preclinical safety information Routine long-term toxicity, effects on reproduction, mutagenicity and carcinogenicity studies have been conducted in test animals. Slight effects of salmon calcitonin were found to be due to its pharmacologic action in toxicity tests. There is no potential risk of embryotoxicity, teratogenicity or mutagenicity. Toxicity and carcinogenicity studies have shown an increased incidence of pituitary tumors in rats when exposed to lower than clinical doses of salmon calcitonin. However, further preclinical studies, particularly carcinogenicity studies in rats, have found that pituitary tumor induction is rat-specific, and the dose of drug given to rats in this test was approximately 760 times greater than the conventional human dose of 50 IU. No adverse reactions associated with pituitary tumors have been observed in patients. Therefore, there is sufficient evidence that pituitary tumor induction is murine-specific, and there is no correlation between murine pituitary tumors and the clinical use of this product.