阿奇霉素滴眼液治疗睑板腺功能障碍的药物遗传学和药代动力学

Syena Damara Riza Gustam
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摘要

睑板腺功能障碍(MGD)是全世界眼表疾病的主要原因,其患病率根据年龄、性别和种族的不同,从3.5%到70%不等。阿奇霉素(Azithromycin, AZM)是一类大环内酯类抗生素,最早是由红霉素衍生而来。临床广泛应用于呼吸道疾病和性传播感染,也可用于眼部疾病。阿奇霉素抑制zymosan1诱导的促炎细胞因子(肿瘤坏死因子α和IL-1β)、趋化因子(IL-6和RANTES)和MMPs (MMP-1、MMP-3和MMP-9) mRNA表达和蛋白产生,提示阿奇霉素可能用于眼表治疗。阿奇霉素通过调节淋巴细胞的趋化性、活化和存活来控制炎症反应的开始和消退。TGF-β1通过抑制肿瘤坏死因子α、IL-1、干扰素γ等促炎细胞因子,在不同细胞类型中发挥抗炎作用。局部AZM溶液1.0%与皮质类固醇(DEX 0.1%)联合治疗2周后MGD的综合治疗效果更好。AZM是最安全的抗生素之一,具有良好的耐受性和特殊的药代动力学性质。此外,它具有广泛的抗菌谱。AZM对许多眼部疾病的治疗有效,在新的眼部感染治疗方案中可作为单一疗法或联合疗法。
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Pharmacogenetics and Pharmacokinetic of Azithromycin Eyedrops in Meibomian Gland Dysfunction Treatment
Meibomian gland dysfunction (MGD) is the leading cause of ocular surface disease throughout the world, which has a prevalence that varied widely from 3.5 to 70% according to age, sex, and ethnicity. Azithromycin (AZM) is the first azalidic antibiotic, a class of macrolide antibiotics, which has derived from erythromycin. It is widely used in clinical practice, not only for respiratory diseases and sexually transmitted infections but also for ocular diseases. azithromycin suppressed zymosan-induced mRNA expression and protein production of proinflammatory cytokines (tumor necrosis factor α and IL-1β), chemokines (IL-6 and RANTES), and MMPs (MMP-1, MMP-3, and MMP-9) by human corneal epithelial cells and suggested the potential for using azithromycin to treat ocular surface It controls the initiation and resolution of inflammatory responses through the regulation of chemotaxis, activation, and survival of lymphocytes. The anti-inflammatory role of TGF-β1 has been recognized in different cell types by inhibiting proinflammatory cytokines including tumor necrosis factor α, IL-1, and interferon γ.The combination of a topical AZM solution 1.0% with corticosteroid (DEX 0.1%) was found superior in the comprehensive treatment of MGD after 2 weeks. AZM is a one of the safest antibiotics, well tolerated, and has special pharmacokinetic properties. Moreover, it has a broad antimicrobial spectrum. AZM is efficacious for the treatment of a  lot of ocular diseases and may be included as monotherapy or in combination therapy in new treatment protocols for more ocular infections.
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