MK-0677, a potent, novel, orally active growth hormone (GH) secretagogue: GH, insulin-like growth factor I, and other hormonal responses in beagles

Endocrinology
T M JacksG Hickey

Abstract

MK-0677, a spiroindoline sulfonamide, is a novel, orally active GH secretagogue. The effects of MK-0677 on serum GH and other hormones after oral and iv single dose administrations in beagles were evaluated. After oral administration in a balanced eight-dog crossover study, treatment with MK-0677 significantly increased peak GH concentrations, with a 5.3-fold increase (mean +/- SEM, 10.5 +/- 1.9 ng/ml) at the 0.25 mg/kg dose, a 9.0-fold increase (18.0 +/- 3.3 ng/ml) at the 0.50 mg/kg dose, and a 15.8-fold increase (31.6 +/- 5.8 ng/ml) at the 1.0 mg/kg dose. Total GH release, expressed as the area under the curve, showed similar significant increases over the effect of the water placebo. A single oral 1 mg/kg dose in three dogs induced a mean GH peak of 27.6 +/- 1.5 ng/ml at 120 min, and GH levels remained elevated up to 360 min after treatment. Insulin-like growth factor I (IGF-I) levels were significantly increased by 30% at 480 min after treatment. Cortisol levels were increased 2.4-fold over pretreatment levels. After i.v. administration, compared to the saline control group which had a mean (+/- SEM) serum GH peak of 3.8 +/- 0.7 ng/ml, MK-0677 at 0.25 mg/kg significantly increased (P < 0.05) peak GH concentrations 20.4-fold...Continue Reading

Citations

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