Antidiuretic effect of Sandostatin® (SMS 201-995) in healthy volunteers

Abstract

Abstract. Ten male healthy volunteers were studied in order to determine whether the synthetic somatostatin analogue Sandostatin® (SMS 201-995) has effects similar to those of natural somatostatin on renal water and electrolyte excretion. The study was carried out in three separate placebo-controlled randomized double-blind cross-over trials. The subjects received single sc injections of 100 μg Sandostatin and placebo under conditions of mild diuresis (trial 1), water load with enhanced diuresis (trial 2), and water load with exogenous lysin-vasopressin (5 IU sc) induced antidiuresis (trial 3). The following parameters were measured: urine flow rate, serum and urine osmolalities, osmolar clearance, free water and creatinine clearances, excretion rates of sodium, potassium, calcium, chloride, and phosphate, and immunoreactive insulin. A marked antidiuretic effect was observed within 2 h after dosing in all three trials. Urine flow rates were reduced by 45% in trial 1 and by 29 and 31% in trials 2 and 3, respectively (all P< 0.05). There were no differences in effects on serum and urine osmolalities between Sandostatin and placebo. Osmolar clearance was significantly reduced in trial 1 (P< 0.01). Free water clearance significantly decreased only in trial 2 (P< 0.05). Sodium excretion decreased by 49, 48 and 67%, respectively, the differences being significant in trials 1 and 3 (P< 0.05). Calcium excretion decreased by 66, 70 and 54% (all P< 0.001). Chloride excretion decreased by 28, 22 and 44%, the differences being significant in trials 2 and 3 (P< 0.05). Potassium excretion, phosphate excretion and creatinine clearance were not significantly altered. These results agree with previous findings with natural somatostatin in man under the condition of high urine flow (trial 2). We suggest that Sandostatin has a direct vasopressin-like effect on the renal tubule. However, the results of trials 1 and 3 are consistent with the involvement of osmolar mechanisms. The question of the clinical relevance of these observations remains open, since during long-term treatment with Sandostatin the drug's antidiuretic effect might be overridden by other mechanisms regulating the water and electrolyte balance.