Sustained suppression of the pituitary-gonadal axis by leuprorelin three-month depot microspheres in rats and dogs.
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) micrograms/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 micrograms/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.
Okada
H
H
DDS Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Doken
Y
Y
Ogawa
Y
Y
Toguchi
H
H
D000818:Animals; D003692:Delayed-Action Preparations; D003864:Depression, Chemical; D004285:Dogs; D005640:Follicle Stimulating Hormone / Q000097:blood; D005837:Genitalia, Male / Q000187:drug effects; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D016729:Leuprolide / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008863:Microspheres; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000187:drug effects*; D013739:Testosterone / Q000097:blood
D003692:Delayed-Action Preparations; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D016729:Leuprolide