UniSA: Clinical and Health Sciences, University of South Australia, GPO Box 2471, Adelaide, South Australia, 5001, Australia.
Quality Use of Medicines and Pharmacy Research Centre, Clinical and Health Sciences, University of South Australia, GPO Box 2471, Adelaide, SA, 5001, Australia.
Pharm Res. 2023 Jun;40(6):1553-1568. doi: 10.1007/s11095-023-03516-x. Epub 2023 May 12.
Chronic Obstructive Pulmonary Disease is characterised by declining lung function and a greater oxidative stress burden due to reduced activity of antioxidant enzymes such as Glutathione Peroxidase 1.
The extent to which drugs may contribute to this compromised activity is largely unknown. An integrative drug safety model explores inhibition of Glutathione Peroxidase 1 by drugs and their association with chronic obstructive pulmonary disease adverse drug events.
In silico molecular modelling approaches were utilised to predict the interactions that drugs have within the active site of Glutathione Peroxidase 1 in both human and bovine models. Similarities of chemical features between approved drugs and the known inhibitor tiopronin were also investigated. Subsequently the Food and Drug Administration Adverse Event System was searched to uncover adverse drug event signals associated with chronic obstructive pulmonary disease.
Statistical and molecular modelling analyses confirmed that the use of several registered drugs, including acetylsalicylic acid and atenolol may be associated with inhibition of Glutathione Peroxidase 1 and chronic obstructive pulmonary disease.
The integration of molecular modelling and pharmacoepidemological data has the potential to advance drug safety science. Ongoing review of medication use and further pharmacoepidemiological and biological analyses are warranted to ensure appropriate use is recommended.
慢性阻塞性肺疾病的特征是肺功能下降和氧化应激负担增加，这是由于抗氧化酶如谷胱甘肽过氧化物酶 1 的活性降低所致。
药物在多大程度上可能导致这种活性降低尚不清楚。综合药物安全模型探讨了药物对谷胱甘肽过氧化物酶 1 的抑制作用及其与慢性阻塞性肺疾病不良药物事件的关系。
利用计算机分子建模方法预测了药物在人及牛模型中谷胱甘肽过氧化物酶 1 活性部位的相互作用。还研究了已批准药物和已知抑制剂硫普罗宁之间的化学特征相似性。随后，搜索了美国食品和药物管理局不良事件系统，以发现与慢性阻塞性肺疾病相关的不良药物事件信号。
统计和分子建模分析证实，包括乙酰水杨酸和阿替洛尔在内的几种已注册药物的使用可能与谷胱甘肽过氧化物酶 1 的抑制和慢性阻塞性肺疾病有关。
分子建模和药物流行病学数据的整合有可能推动药物安全科学的发展。有必要对药物使用情况进行持续审查，并进一步进行药物流行病学和生物学分析，以确保推荐的使用方法是恰当的。
