Pharmaceutical Research

, Volume 8, Issue 5, pp 584–587 | Cite as

Sustained Pharmacological Activities in Rats Following Single and Repeated Administration of Once-a-Month Injectable Microspheres of Leuprolide Acetate

  • Hiroaki Okada
  • Toshiro Heya
  • Yasuaki Ogawa
  • Hajime Toguchi
  • Tsugio Shimamoto


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.

leuprolide (leuprorelin) once-a-month injectable microspheres gonadotropin suppression steroidogenesis inhibition repeated administration 


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Copyright information

© Plenum Publishing Corporation 1991

Authors and Affiliations

  • Hiroaki Okada
    • 1
  • Toshiro Heya
    • 1
  • Yasuaki Ogawa
    • 1
  • Hajime Toguchi
    • 1
  • Tsugio Shimamoto
    • 1
  1. 1.Pharmaceutics Research LaboratoriesTakeda Chemical Industries, Ltd.YodogawaJapan

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