Mehta Dharmini C, Short Jennifer L, Hilmer Sarah N, Nicolazzo Joseph A
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.
Pharm Res. 2015 Mar;32(3):819-39. doi: 10.1007/s11095-014-1522-0. Epub 2014 Oct 16.
Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by β-amyloid plaques and hyperphosphorylated tau tangles in the brain. Alongside these pathological lesions, there have been multiple reports of physical and biochemical alterations to the blood-brain barrier (BBB) in people with AD, potentially impacting on the ability of systemically-administered drugs to reach the brain parenchyma. Though there has been much research into the identification of these BBB alterations during AD, there are very few studies that have assessed the impact of such BBB changes on the ability of therapeutic agents to traverse the BBB. Due to their increased age-associated risk of chronic disease, most people with AD are prescribed multiple concurrent medications. In people with AD, the altered nature of the BBB could impact upon the disposition and therefore pharmacological effects of a wide range of medicines. This review therefore evaluates the impact of BBB alterations in AD on CNS drug exposure, along with relevant examples of preclinical and clinical studies that address this current issue. This review highlights that the CNS exposure of drugs is likely to differ between people with AD and healthy individuals, warranting further clinical investigations and the consideration to tailor dosing regimens in people with this neurodegenerative disorder.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是大脑中出现β-淀粉样蛋白斑块和过度磷酸化的tau缠结。除了这些病理病变外，已有多项报道称AD患者的血脑屏障（BBB）存在物理和生化改变，这可能会影响全身给药药物到达脑实质的能力。尽管在AD期间对这些血脑屏障改变的识别进行了大量研究，但很少有研究评估这种血脑屏障变化对治疗药物穿越血脑屏障能力的影响。由于AD患者与年龄相关的慢性病风险增加，大多数患者会同时服用多种药物。在AD患者中，血脑屏障的改变性质可能会影响多种药物的处置，进而影响其药理作用。因此，本综述评估了AD患者血脑屏障改变对中枢神经系统（CNS）药物暴露的影响，并列举了相关的临床前和临床研究实例以解决当前这一问题。本综述强调，AD患者与健康个体的中枢神经系统药物暴露情况可能不同，这需要进一步的临床研究，并考虑为这种神经退行性疾病患者量身定制给药方案。
