PHARMACOKINETIC STUDY AND EFFECTS ON GROWTH-HORMONE SECRETION IN HEALTHY-VOLUNTEERS OF THE NEW SOMATOSTATIN ANALOG BIM23014

We have studied the pharmacokinetics and the effects of BIM 23014 (BIM), a new, long-acting octapeptide somatostatin analogue, on basal and stimulated GH secretion in normal men. BIM 250 gg sc significantly reduced a GHRH-induced increase in plasma GH. The continuous sc administration of BIM for 24 h dramatically blunted spontaneous GH secretion; 2000 and 3000 mug daily reduced GH secretion to a greater extent than 1000 mug daily. During these experiments a significant negative correlation (r - 0.66) was found between plasma GH and BIM levels. Acute sc administration of 1000 mug BIM significantly reduced the rise in plasma GH observed in the second part of the oral glucose tolerance test. Plasma BIM levels peaked around 30 min, and the elimination half life was 90 min. Plasma BIM levels were below 1 ng/ml 6 h after the injection of 1000 mug BIM, and at that time GH started to rise again. We conclude that BIM 23014 250 to 1000 mug sc is able to reduce the plasma GH response to GHRH or to the fall in glucose following an oral glucose tolerance test; a constant infusion of BIM, in doses 1000 mug daily, dramatically suppresses spontaneous GH secretion; 2000 mug/day by chronic subcutaneous infusion was the most effective dose of BIM in the suppression of GH secretion, and was associated only with minor adverse effects.