Sustained pharmacological activities in rats following single and repeated administration of once-a-month injectable microspheres of leuprolide acetate

• Published in: Pharmaceutical research 1991-05, Vol.8 (5), p.584-587
• Main Authors: OKADA, H, HEYA, T, OGAWA, Y, TOGUCHI, H, SHIMAMOTO, T
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Delayed-Action Preparations; Follicle Stimulating Hormone - blood; General pharmacology; Gonadotropin-Releasing Hormone - administration & dosage; Gonadotropin-Releasing Hormone - analogs & derivatives; Gonadotropin-Releasing Hormone - pharmacokinetics; Gonadotropin-Releasing Hormone - pharmacology; Hormones - administration & dosage; Hormones - pharmacokinetics; Hormones - pharmacology; Injections, Subcutaneous; Leuprolide; Luteinizing Hormone - blood; Male; Medical sciences; Microspheres; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Rats; Rats, Inbred Strains; Testosterone - blood; Time Factors
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/a:1015844421319

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.