在人类中,N-乙-D-曼诺胺的绝对生物可用性和静脉注射药理学
Tahlia R Meola1, Guy Ludbrook2, Gianfranco Fornasini3
1UniSA Clinical & Health Sciences, University of South Australia, Adelaide, SA, Australia.
British journal of clinical pharmacology
|September 19, 2025
概括
由于吸收不良,N-乙-D-曼诺胺单 (ManNAc) 的口服生物利用率非常低 (4.01%),可能是由于其高极性. 这就解释了为什么ManNAc的系统暴露与剂量不成比例地增加.
科学领域:
- 药理动力学 药理动力学
- 药物的新陈代谢和处置
- 生物化学 生化学
背景情况:
- N-乙-D-曼诺胺单 (ManNAc) 显示了对GNE肌病的治疗潜力.
- 曼纳克的绝对生物可用性和药理动力学需要进一步研究.
研究的目的:
- 为了确定静脉注射ManNAc的药理动力学.
- 为了描述口服ManNAc.c.的绝对生物利用性.
主要方法:
- 在一项对6名健康男性进行的交叉研究中,单次口服 (1000毫克) 和静脉注射 (100毫克) 的ManNAc剂量.
- 血ManNAc度在48小时内得到量化.
- 进行了非分组的药理动力学分析.
主要成果:
- 静脉注射ManNAc的清除值为10.1L/h,分布量为24.1L,半衰期为1.67h.
- ManNAc的平均绝对口服生物利用率为4.01%.
- 在最初的3小时内,零级吸收量约为10毫克/小时.
结论:
- 由于高极性,ManNAc的低口服生物可用性是由于吸收不良而导致的.
- 零级吸收解释了剂量独立的全身暴露增加.
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