肥胖女性中甲福林度降低 患有人类免疫缺陷病毒的肥胖女性用多卢特格拉维尔治疗
Roland van Rensburg1, Tracy Kellermann1, Veshni Pillay-Fuentes Lorente1
1Division of Clinical Pharmacology, Department of Medicine, Stellenbosch University, Cape Town, South Africa.
The Journal of infectious diseases
|June 5, 2025
概括
服用杜洛特格拉维尔和甲胺的艾滋病毒感染肥胖妇女可能会在当前的1000mg甲胺限量下低于剂量. 肥胖个体中较低的杜洛泰格拉维尔水平可以降低甲胺的含量.
科学领域:
- 药理动力学 药理动力学
- 艾滋病毒/艾滋病管理
- 肥胖医学 肥胖医学
背景情况:
- 肥胖在艾滋病毒感染女性 (WWH) 中普遍存在,增加了失糖症的风险.
- 目前的指导方针建议将甲福明限制在1000mg/天与多卢特格拉维尔,因为药理学相互作用.
- 之前的研究表明,杜洛特格拉维尔会增加甲胺的暴露,但在肥胖的WWH中缺乏数据.
研究的目的:
- 评估在肥胖的WWH中甲福明和多卢特格拉维尔的药理动力学.
- 评估肥胖对该人口药物暴露的影响.
- 为结合疗法中肥胖的WWH提供剂量建议.
主要方法:
- 在15名肥胖的WWH患者中进行密集的血采样,他们接受稳定的甲福明 (1000毫克/天) 和多洛特格拉维尔 (50毫克/天) 治疗.
- 双能X射线吸收计用于身体脂肪成分分析.
- 与参考研究相比,药物度的非分区分析.
主要成果:
- 肥胖的WWH与非肥胖个体相比,甲胺暴露率降低了40.9%,杜洛特格拉维尔暴露率降低了54.4% (AUC0-24).
- 在肥胖的WWH中,甲胺和杜洛泰格拉维尔清除值显著更高 (分别是1.7倍和2.2倍).
- 身体脂肪成分和药物暴露之间没有发现任何关联.
结论:
- 每天1000毫克的甲福林剂量可能不足以治疗多卢特格拉维尔的肥胖的WWH,从而导致潜在的低剂量.
- 在肥胖个体中,较低的杜洛特格拉维尔度可能会降低其对甲福林清除的抑制作用.
- 为了确保最佳的治疗结果,目前对肥胖WWH的甲福明剂量限制应该进行修订.
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