艾西克洛维尔在中枢神经系统部分的分布:一种猪的药理动力学模型
T Mariager1,2,3, J H Terkelsen2, J M Guldbæk1,3
1Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark.
Antimicrobial agents and chemotherapy
|July 9, 2025
概括
静脉注射的阿西克洛维尔 (ACV) 在第二剂后在中枢神经系统 (CNS) 中达到治疗性水平,用于治疗简单疹病毒 (HSV) 脑炎. 初始剂量可能需要调整以获得最佳疗效.
科学领域:
- 药理学 药理学是指药理学的学科.
- 传染性疾病 传染性疾病
- 神经科学是一个神经科学.
背景情况:
- 简单疹病毒 (HSV) 脑炎是一种严重的感染,具有显著的死亡率和神经系统风险.
- 静脉注射阿西克洛维尔 (ACV) 是标准治疗方法,但其透到中枢神经系统 (CNS) 需要进一步阐明.
研究的目的:
- 通过使用猪模型,评估阿西克洛维尔 (ACV) 在中枢神经系统各个区域的药理动力学分布.
- 为了确定标准ACV剂量是否达到治疗HSV脑炎的目标度.
主要方法:
- 使用猪模型,两组接受单次或多次静脉注射ACV剂量 (10 mg/kg).
- 微透析采样在皮层和皮层下细胞外液 (ECF) 和心室/脑脊液 (CSF) 中的未结合的ACV度.
- 药物动力学参数 (fCmax,T > IC50,AUC) 与HSV-1 IC50值 (0.56μg/mL) 相比进行了分析.
主要成果:
- 在第二次和第三次剂量后,在所有中枢神经系统区间中实现了目标ACV度 (fCmax>0.56μg/mL).
- 超过IC50的时间 (T > IC50) 和曲线下的面积 (AUC) 随着随后的剂量增加,并且在中央神经系统区间一致.
- 脑内透率 (fAUCtissue/fAPlasma) 在第三次剂量间隔期间从0.18到0.32不等.
结论:
- 在猪的第二剂后,每8小时服用10毫克/公斤的静脉注射ACV达到中枢神经系统的治疗水平,支持当前的HSV脑炎治疗方案.
- 最初的ACV剂量可能无法达到治疗水平,建议考虑使用更高的初始剂量或长时间输注.
- 需要在炎症条件下进行进一步的研究,以确认这些发现及其临床适用性.
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