Sustained Suppression of the Pituitary-Gonadal Axis by Leuprorelin Three-Month Depot Microspheres in Rats and Dogs

Abstract

The pharmacological effects of leuprorelin three-month depot microspheres were investigated in rats and dogs. After s.c. and i.m. injection, the microspheres provided similar linear drug release and sustained serum drug levels for 3 months. Persistent suppression of serum LH, FSH (in rats) and testosterone (in rats and dogs) for over 16 weeks was achieved when the microspheres were given at a dose of 100 (rat) and 25.6 (dog) µg/kg/day. These hormone release responses upon periodic challenge tests revealed that a single injection of the microspheres caused dramatic suppression of the function of the pituitary-gonadal system for 15 weeks in rats. The growth of the genital organs was also suppressed dose-dependently by injection of the microspheres over 3 months; the strongest suppression was achieved at a dose of 100 µg/kg/day. This three-month depot formulation is expected to be more convenient than the one-month depot with improved patient compliance and therapeutic effects.