Efficacy, pharmacokinetics and tolerability of a somatostatin analogue (L-363,586) in insulin-dependent diabetes mellitus |
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Authors: | I Gottesman J Tobert R Vandlen J Gerich |
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Institution: | 1. Polymer Reaction Engineering Group, INTEC (Universidad Nacional del Litoral-CONICET), Güemes 3450, Santa Fe 3000, Argentina;2. POLYMAT, Kimika Aplikatua Saila, Kimika Fakultatea, University of the Basque Country UPV/EHU, Joxe Mari Korta Zentroa, Tolosa Hiribidea 72, 20018 Donostia-San Sebastian, Spain;3. Facultad de Ingeniería Química (Universidad Nacional del Litoral), Santiago del Estero 2829, Santa Fe 3000, Argentina |
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Abstract: | To assess the pharmacologic properties and possible use in the treatment of diabetes mellitus of a recently developed analogue somatostatin (L-363,586), the analogue (2, 5, 10 or 40 micrograms/hr), somatostatin (200 micrograms/hr), or placebo were infused intravenously for 5 hours in 6 insulin-dependent diabetic subjects who were given a standard meal containing xylose. The metabolic clearance rate of the analogue (approximately 300 ml/min) was 1/6 that previously reported for somatostatin (approximately 2000 ml/min) and its half-life was approximately 20 times as great as that reported for somatostatin (45 vs 2 min). At a dose of 10 micrograms/hr, the analogue produced suppression of plasma glucagon, growth hormone, glucose, xylose and triglyceride responses to meal ingestion which were comparable to those observed when somatostatin was infused at a rate of 200 micrograms/hr. We conclude that L-363,586 is a long-acting and potent analogue of somatostatin, which has the potential for use as an adjunct to insulin in the treatment of diabetes mellitus. |
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