Oral Properties of MK0677 in the Clinic

Based on the indications of potency, duration of action, oral bioavailability, and selectivity, which are summarized above, compound 44 (L-163,191) as its crystalline mesylate salt was selected for safety assessment studies. Subsequently it entered clinical testing and was given the designation MK-0677 as a potential product candidate. In confirmation of the animal data, MK-0677 was found to raise IGF-1 in man following oral administration. The first published account was by Copinischi et al. (62) who treated nine healthy young men daily for seven days in a crossover comparison of placebo and 5- and 25-mg doses of MK-0677. IGF-1 levels were increased in a dose dependent manner without detectable elevations of GH. Nor was any evidence observed of induced hypercortisolism. Chapman et al. (63) reported results shortly thereafter of a study in which 32 healthy elderly men and women received placebo, or 2, 10, or 25 mg MK-0677 orally, once daily for two separate study periods of 14 and 28 days. Dose-dependent increases in GH and IGF-1 were observed. Remarkably, the dose of 25 mg/day of MK-0677 in most of these subjects brought serum IGF-1 levels into the range seen in young adults. In this study also plasma and urinary cortisol levels were similar in all groups.

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