Sustained pharmacological activities in rats following single and repeated administration of once-a-month injectable microspheres of leuprolide acetate.
Once-a-month injectable microspheres of leuprolide acetate prepared with copoly(DL-lactic/glycolic acid) using an in-water drying method were assessed for duration of the analogue release and pharmacological effects in rats after a single or repeated injection. The periodic challenge test revealed that a single injection of the microspheres caused a dramatic and persistent suppression of the ability of the pituitary-gonadal system to secrete gonadotropin and testosterone for over 5 weeks. The complete recovery of these functions was observed 10 weeks after the injection. The repeated injection of the microspheres at intervals of 2 or 4 weeks achieved persistent suppression of steroidogenesis after an initial transient flare-up and beneficially avoided the "acute-on-chronic response." This depot formulation is expected to assure patient compliance and produce stronger therapeutic effects than the daily solution.
Okada
H
H
Pharmaceutics Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Heya
T
T
Ogawa
Y
Y
Toguchi
H
H
Shimamoto
T
T
D000818:Animals; D003692:Delayed-Action Preparations; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D006728:Hormones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D007279:Injections, Subcutaneous; D016729:Leuprolide; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008863:Microspheres; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000097:blood; D013997:Time Factors
D003692:Delayed-Action Preparations; D006728:Hormones; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D016729:Leuprolide