acyline and Pruritus

Acyline is a novel GnRH antagonist found in animal studies to be a potent suppressor of circulating gonadotropin and testosterone (T) levels. We conducted the first study of acyline administration to humans. Eight healthy, eugonadal young men were administered a series of acyline injections (0, 2.5, 7.5, 25, and 75 microg/kg), each injection separated by at least 10 d. Serum FSH, LH, and T levels were measured for 7 d after injections. Acyline suppressed FSH, LH, and T levels in a dose-dependent fashion. Maximal suppression occurred after injection of 75 microg/kg acyline, which suppressed FSH to 46.9 +/- 2.5%, LH to 12.4 +/- 2.2%, and T to 13.4 +/- 1.4% of baseline levels, maintaining suppression for over 48 h. Serum acyline levels peaked at 1 h at 18.9 +/- 0.9 ng/ml, remained significantly elevated above background 7 d after injection, and returned to background levels by 14-17 d after injection. Side-effects at the site of injection were limited to infrequent blush and pruritus that resolved within 90 min of injection. Higher doses of acyline might be effective as depot injections for long-lasting gonadotropin suppression in hormone-dependent diseases and for use in male hormonal contraception regimens.

Topics: Adult; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Male; Oligopeptides; Pruritus; Safety; Skin; Testosterone

Acyline is a novel GnRH antagonist that reliably inhibits gonadotropins and testosterone (T) levels in men for 48 h after a single dose up to 75 microg/kg. In this study we examined gonadotropin and T levels in 28 healthy young men administered acyline as single doses of 150 or 300 microg/kg or serial injections of 75 microg/kg. A single 300 microg/kg dose of acyline suppressed gonadotropins and T to castrate levels for 15 d (baseline, 21.1 +/- 3.1; nadir, 1.95 +/- 0.4 nmol/liter; mean +/- sem; P < 0.05). Serum acyline levels peaked 90 min after the injection of 300 microg/kg acyline to a maximum concentration of 112.4 +/- 18 ng/ml (n = 7; t(1/2) = 4.9 d). Injections of 75 microg/kg acyline every 2 d for five doses suppressed gonadotropins for more than 20 d (nadir T, 1.06 +/- 0.17 nmol/liter; P < 0.05 compared with baseline). Adverse events were mild and included erythema and pruritus at the injection site. Acyline, therefore, is one of the most potent peptide GnRH antagonists studied to date with minimal adverse events. A twice monthly injection of acyline could be used as a potent suppressor of the GnRH axis to advance the development of a hormonal male contraceptive or for treatment of hormonally dependent disease.

Topics: Adult; Drug Administration Schedule; Erythema; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Injections, Subcutaneous; Male; Middle Aged; Oligopeptides; Pruritus; Reference Values; Testosterone; Time Factors