DOES DESENSITIZATION TO HEXARELIN OCCUR

Hexarelin, a potent growth hormone (GH)-releasing peptide, is capable of causing profound GH release in normal individuals. If the GH respon se to hexarelin in humans becomes appreciably attenuated following lon g-term administration, this would seriously limit the potential therap eutic use of hexarelin and similar agents. The effect of twice-daily s ubcutaneous injections of hexarelin on GH release was therefore invest igated over a period of 16 weeks in 12 healthy elderly individuals. Th e mean (+/- SEM) areas under the GH curve (AUC(GH)) at weeks 0, 1, 4 a nd 16 were 19.1 +/- 2.4, 13.1 +/- 2.3, 12.3 +/- 2.4 and 10.5 +/- 1.8 m u g/l/hour, respectively. There was a significant change in AUG(GH) ov er the study period (P = 0.0003), Further analysis showed that the dec reases in AUG(GH) at weeks 4 and 16 were significant (P 4 0.05 and P < 0.01, respectively) compared with baseline values. Four weeks after c ompletion of the 16-week study period, hexarelin was again administere d. On this occasion, AUG(GH) increased significantly compared with tha t at week 16 (from 10.5 +/- 1.8 to 19.4 +/- 3.7 mu g/l/hour; P < 0.05) and was not significantly different compared with that at week 0. The se results show that attenuation of the GH response after long-term he xarelin therapy is partial and reversible.