The effect of rectal and nasal administration of salmon calcitonin in normal subjects

Abstract

In order to ascertain the blood levels and the biologic responses obtained after administration of two noninjectable forms of salmon calcitonin (SCT) (i.e., a nasal spray and a suppository), two doses of 200 IU each were administered at 3 hour intervals nasally to 8 normal subjects, and rectally to 9 normal subjects. Five untreated subjects served as controls. All were given a standardized diet for 2 days before the test. Plasma salmon-calcitonin, ionized calcium, phosphate, sodium, proteins, creatinine, and alkaline phosphatase were measured repeatedly after the administration of the drug. Modifications in fractionated urinary calcium, phosphate, sodium, and creatinine excretions (and hydroxyproline for the 8 subjects treated by the nasal spray) were compared with the values measured on the previous day. Plasma concentrations of SCT were found to increase sharply with both routes of administration, the peaks being high and short after rectal administration, low but more sustained after nasal application. Despite these differences, almost similar biologic effects could be demonstrated: transient hypocalcemia, increased calciuria, phosphaturia, and natriuria. Urinary hydroxyproline excretion decreased. Plasma sodium did not increase, whereas it did in the controls. In conclusion, nasal sprays and suppositories of SCT appear to exert the known biologic effects of SCT, and might be favored for long-term treatment in diseases representing indications for calcitonin therapy.

PK/PD modelling of comb-shaped PEGylated salmon calcitonin conjugates of differing molecular weights

“…administration [37]. The non-linear relationship between serum calcium reduction and [sCT] suggests a highly complex relationship [21,38], and there is obvious difficulty in rank-ordering formulations when the window of the calcium reduction is so narrow. Thus, measurement of serum [sCT] is the more sensitive screening assay.…”

Acute effects of nasal salmon calcitonin on calcium and bone metabolism

“…Urine was sampled through 26 hours for the periods 08.00-10.00 (08-10), 10.00-12.00 (10-12), 12.00-15.00 (12)(13)(14)(15), and 15.00--08.00 (15-08), and 08.00-10.00 the next morning (08-10)#. Sampling intervals were chosen based on the study by Buclin et al [9]. One day prior to administration of the nasal spray and through the study period the participants were kept on a low-calcium and collagen-free diet whereas water intake was not restricted.…”

“…The data available suggest that nasal CT slightly decreases urinary OH-proline in the hours immediately after administration, but gives rise to a paradoxical elevation in urinary OH-proline later on [8,9]. When evaluated by urinary nondialyzable polypeptides containing OH-proline and by serum levels of the carboxyterminal propeptide of type 1 procollagen (PICP), bone formation may decrease in parallel to bone resorption after injection of CT [1,3], whereas there are no reports of the acute effects of nasal CT on bone formation.…”

Effect of calcitonin on bone healing following titanium implant insertion.

“…In the present study, it was observed that calcitonin administration to healthy animals impaired initial bone healing (0-6 weeks) following dental implant insertion. Thus, it can be assumed, as reported by Buclin et al (1987) (14), that calcitonin produces its biological effects in healthy animals, althought Avioli (1991) (15) reported that the calcitonin effects could be observed only in individuals with bone metabolism disorders. It may be observed that, in the present study, antibody was not able to neutralize the biological effects of the calcitonin, as previously reported (16).…”

“…Antibiotics were not administered. The animals were sacrificed by an overdose of urethane® (7,14,21,28 and 42 days after the surgical procedures), at each time point, i.e., there were 3 animals for the test group and 3 animals for the control group for each period. The femurs were dissected and fixed in 10% formal saline for 48 hours.…”