H. Okada et al., SUSTAINED SUPPRESSION OF THE PITUITARY-GONADAL AXIS BY LEUPRORELIN 3-MONTH DEPOT MICROSPHERES IN RATS AND DOGS, Pharmaceutical research, 11(8), 1994, pp. 1199-1203
The pharmacological effects of leuprorelin three-month depot microsphe
res were investigated in rats and dogs. After s.c. and i.m. injection,
the microspheres provided similar linear drug release and sustained s
erum drug levels for 3 months. Persistent suppression of serum LH, FSH
(in rats) and testosterone (in rats and dogs) for over 16 weeks was a
chieved when the microspheres were given at a dose of 100 (rat) and 25
.6 (dog) mu g/kg/day. These hormone release responses upon periodic ch
allenge tests revealed that a single injection of the microspheres cau
sed dramatic suppression of the function of the pituitary-gonadal syst
em for 15 weeks in rats. The growth of the genital organs was also sup
pressed dose-dependently by injection of the microspheres over 3 month
s; the strongest suppression was achieved at a dose of 100 mu g/kg/day
. This three-month depot formulation is expected to be more convenient
than the one-month depot with improved patient compliance and therape
utic effects.