title: Formulation study of leuprorelin acetate to improve clinical performance.
abstract: Leuprorelin acetate, a highly potent gonadotrophin-releasing hormone agonist, was originally launched in the USA as a daily injection for the treatment of metastatic prostatic cancer. A once-monthly injectable depot form was subsequently developed. Biodegradable copoly(DL-lactic/glycolic) acid was chosen as the release-controlling polymer, and microspheres containing leuprorelin acetate were prepared by the in-water drying method. Results of studies in rats showed that a copolymer with a molecular weight of 14,000 and a lactic/glycolic acid ratio of 75/25 had the most satisfactory release-controlling properties. Microspheres given once monthly reduced serum testosterone levels in male rats. Microspheres also reduced serum oestradiol levels and caused a marked regression in experimental endometriosis in female rats. In clinical studies of prostatic cancer, use of the depot formulation has effectively reduced the dose required to as low as one-eighth of that needed for administration by daily injection. A sophisticated manufacturing system has now been developed and products now available have many advantages.
authors.affiliation: Pharmaceutics Research Laboratories, Takeda Chemical Industries Ltd., Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Toguchi
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004715:Endometriosis / Q000188:drug therapy; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D016729:Leuprolide / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use; D008297:Male; D008863:Microspheres; D011471:Prostatic Neoplasms / Q000188:drug therapy; D051381:Rats; D013739:Testosterone / Q000097:blood
chemical_list: D003692:Delayed-Action Preparations; D013739:Testosterone; D016729:Leuprolide