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  • Author: Peter A. van Liessum x
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Peter A. van Liessum, Gerlach F. Pieters, Anthony G. Smals, Ad R. Hermus, TheoJ. Benraad and Peter W. Kloppenborg

Abstract.

The recommended dosage schedules for intermittent sc therapy with the somatostatin analogue octreotide in acromegaly vary widely, from 100 to 1500 μg daily. As acute administration of octreotide has been shown to predict its long-term response, we performed a single-dose response study in 5 patients with active acromegaly using doses of 25, 50, 100, 200 and 400 μg octreotide as well as a placebo injection. Plasma GH of 2 patients did not normalize after any of the injections, but nadir plasma GH overall gradually decreased as doses were increased from 25 to 400 μg. The 400 μg octreotide dose was superior with regard to the duration of plasma GH suppression to below 5 μg/l or 25% of the basal GH level, the mean GH as a percentage of the basal level over the first 4 and 8 h, and the integrated reduction of plasma GH during the first 4 and 8 h. The postprandial integrated insulin secretion during the first 3 h after injection of the octapeptide was significantly lower after 50, 100 and 400 μg than after the placebo injection. The mean plasma glucose as a percentage of the basal level during the first 8 h was significantly higher after octreotide after the 200 and 400 μg injections. Minor adverse events were seen in 2 patients after injection of 200 and 400 μg octreotide. Within the limitations of this single-dose response study it was concluded that injection of 400 μg octreotide yields the best results with regard to suppression of GH secretion, whereas the 50, 100 and 200 μg doses are superior to 25 μg, but do not differ from each other.

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Peter A. van Liessum, Leon M. Swinkels, Gerlach F. Pieters, Alec A. Ross, Anthony G. Smals, Theo J. Benraad and Peter W. Kloppenborg

Abstract

Serum samples from 13 patients with active acromegaly on long-term sc treatment with octreotide (SMS 201-995, 1-36 months, mean daily dose 285 μg) were taken 12 h after the injection of their regular evening doses. Octreotide assay was performed using 125I-Tyr-SMS and a polyclonal rabbit anti-serum. For assessment of antibody formation both serum coated charcoal adsorption (adsorption of free octreotide) and polyethylene glycol precipitation (precipitation of IgG complexes) were used. The mean binding percentage in the patients proved to be similar to that of 5 healthy volunteers (p>0.10). No specific binding was detected, whatever method used. No correlation was found between the binding percentages and octreotide serum levels, duration of octreotide treatment or daily octreotide dose (p>0.10). These results strongly suggest that clinically relevant endogenous antibody formation is not a frequent event during long-term sc treatment of acromegalic patients with octreotide.