Delayed release formulation of the somatostatin analog rc-160 inhibits the growth hormone (GH) response to gh-releasing factor-(1-29)nh2 and decreases elevated prolactin levels in rats

Recently, we have developed a long-acting delivery system for our somatostatin (SS) analog RC-160 based on injectable microcapsules in poly-(D,L-lactide-coglycolide). We studied the capacity of this formulation to repeatedly block the GH secretion induced by administration of GRF-(1-29)NH₂ (GRF) on different days. Male rats anesthetized with pentobarbital were injected iv with 2.5 μg/kg BW GRF-(1-29)NH₂ or saline. Five minutes later, blood samples were taken for GH measurement, and the animals were injected im with RC-160 microcapsules at a dose calculated to release 25 μg/day of the analog for 7 days or with the vehicle. The GRF stimuli were repeated 48 h, 96 h, and 8 days after administration of SS analog in microcapsules. GRF administration increased GH levels at the four times tested (P < 0.01) in the control group injected with vehicle, while RC-160 microcapsules inhibited the GH response for more than 96 h (P < 0.01). The GH levels augmented by pentobarbital were also decreased by the RC-160 microcapsules (P < 0.01). Animals treated with microcapsules showed smaller increases in their body weight than untreated rats (P < 0.05). We also investigated the effect of RC-160 microcapsules on hyperprolactinemic female rats implanted with pituitary glands under the kidney capsules. High PRL levels in rats bearing pituitary grafts showed a significant decrease when measured 4 days after the administration of RC-160 microcapsules. These results demonstrate the efficacy of the long-acting delivery system of the SS analog RC-160 and suggest the possible clinical usefulness of this formulation for lowering GH and PRL levels.