Okada H, Doken Y, Ogawa Y, Toguchi H
DDS Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Pharm Res. 1994 Aug;11(8):1199-203. doi: 10.1023/a:1018905403359.
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.
在大鼠和犬中研究了亮丙瑞林三个月长效微球的药理作用。皮下注射和肌肉注射后，微球呈现相似的线性药物释放，并使血清药物水平维持3个月。当微球以100（大鼠）和25.6（犬）微克/千克/天的剂量给药时，血清促黄体生成素、促卵泡激素（大鼠）和睾酮（大鼠和犬）持续抑制超过16周。这些在定期激发试验中的激素释放反应表明，单次注射微球可使大鼠垂体 - 性腺系统功能显著抑制15周。在3个月内注射微球，生殖器官的生长也呈剂量依赖性受到抑制；在100微克/千克/天的剂量下抑制作用最强。这种三个月长效制剂预计比一个月长效制剂更方便，可提高患者的依从性和治疗效果。
