Plasma Kinetics and Acute Effects of Pharmacologic Doses of Porcine Calcitonin in Man

Abstract

Plasma kinetics of a pharmacologic dose of porcine calcitonin (PCT) in man were investigated using a sensitive radioimmunoassay. A single intravenous injection of 1 mg of homogeneous PCT was given to 21 subjects (5 normal, 6 with osteoporosis, 5 with hyperparathyroidism and 5 with Paget's disease) and a continuous prolonged infusion was given to 5 normal subjects. Plasma disappearance after single injection or continuous infusion could be described as a sum of at least 2 exponential components with half-times of 2.4 (0.3) and 40.9 (6.2) min (mean and se). Metabolic clearance rate during continuous infusion was 846 (42) ml/min. The apparent volume of distribution was 21.4 (2.0)% of body weight. Substantial hypocalcemia was associated, in 4 of 5 patients with Paget's disease, with an increase in serum immunoreactive parathyroid hormone (iPTH) which was sustained for the duration of the hypocalcemia; in the other groups these responses were equivocal or absent. However, injection of homogeneous PCT suppressed the diurnal increase of iPTH observed on the control day in the normal group. During the 4 hr after the injection, urinary hydroxyproline excretion decreased in all but 3 of 18 patients. Urinary phosphate excretion increased significantly (p <0.05), but the slight increases in urinary excretion of calcium, magnesium, sodium and potassium were not statistically significant.