MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism.

摘要: The reversal of diet-induced negative nitrogen balance by GH suggests a possible therapeutic role for treatment in catabolic patients. A double-blind, randomized, placebo-controlled, two-period cross-over study was designed to investigate whether MK-677, an orally active nonpeptide mimic GH-releasing peptide, can reverse protein catabolism. Eight healthy volunteers (ages 24-39 yr) were calorically restricted (18 kcal/kg.day) two 14-day periods. During the last 7 days each diet period, subjects received either oral MK-677 25 mg or placebo once daily. There 14- 21-day washout interval between first week caloric restriction (i.e. alone), daily losses similar both groups (mean +/- SE; group -2.67 0.40 g/day vs. -2.83 0.26 g/day). second (diet and drug), mean 0.31 0.21 compared with -1.48 (P < 0.01). improved integrated over treatment; area under curve day 8-14 response +2.69 5.0 (SE) -8.97 5.26 g.day 0.001). produced peak 55.9 31.7 micrograms/L after single dose (day 1 treatment) 22.6 9.3 dosing values approximately 9 (treatment 1) 7). Following initial 7-day restriction, insulin-like growth factor-I (IGF-I) declined from 232 186 19 ng/mL 236 174 23 group. Mean IGF-I concentration increased significantly during 264 31 5 188 No significant difference IGF binding protein-2 found treatments. However, protein-3 also 3273 330 SE) 2604 253 Neither serum cortisol nor PRL greater placebo. (25 mg) generally well tolerated without clinically adverse experiences. In conclusion, reverses wasting, suggesting that if these short-term anabolic effects are maintained patients who because certain acute chronic disease states, it may be useful treating conditions.