SUSTAINED ELEVATED SERUM SOMATOTROPIN CONCENTRATIONS IN HOLSTEIN STEERS FOLLOWING SUBCUTANEOUS DELIVERY OF A GROWTH-HORMONE RELEASING-FACTOR ANALOG DISPERSED IN WATER, OIL OR MICROSPHERES
Tp. Foster et al., SUSTAINED ELEVATED SERUM SOMATOTROPIN CONCENTRATIONS IN HOLSTEIN STEERS FOLLOWING SUBCUTANEOUS DELIVERY OF A GROWTH-HORMONE RELEASING-FACTOR ANALOG DISPERSED IN WATER, OIL OR MICROSPHERES, Journal of controlled release, 47(1), 1997, pp. 91-99
Growth hormone releasing factor (GRF) stimulates pituitary somatotropi
n (ST) release. Somatotropin directly or indirectly through insulin li
ke-growth factor I decreases lipogenesis and promotes protein accretio
n resulting in enhanced growth in food producing animals such as cattl
e and swine. A sustained release formulation is required to capitalize
on GRF biological properties since frequent animal handling in a prod
uction facility is difficult. Sustained durations were evaluated with
aqueous, oil and microsphere suspensions containing a previously disco
vered metabolic stable growth hormone releasing factor analog 8,28),Al
a(15),Leu(27),Hse(30)bGRF(1-30)-NH-ethyl). Serum ST concentrations wer
e measured periodically during a 35-day period after the formulations
were administered to meal-fed Holstein steers. Areas under the ST dail
y curves (ST-AUC) formed the basis for determining the time daily ST-A
UG returned to baseline for each treatment group. Time to return to ba
seline was 21 days when delivering subcutaneously a 200 or 400 mg dose
of a 20% oil suspension and 14 days for a 200 mg dose at 10% load in
poly(lactide-co-glycolide) microspheres. The longest duration, 35 days
, was achieved with a 200 mg dose of an 18% aqueous nanosuspension. A
zero-order release was observed with the 18% aqueous formulation as in
dicated by the ST-AUC not changing from days 7 through 35. Formation o
f fibrils and subsequent dissolution from the fibrils was thought impo
rtant in sustaining the drug release.