目的:管理药物-食品相互作用对于优化喹诺酮类药物的有效性和安全性至关重要。按照PRISMA准则,我们系统综述了饮食干预对22种喹诺酮类药物生物利用度的影响.
方法:所有描述或调查食物影响的研究,饮料,抗酸剂,和矿物质补充剂对口服喹诺酮类药物的药代动力学参数或药代动力学/药效学指标的影响被考虑在内。我们排除了评论,体外和计算机模拟研究,对动物进行的研究,和那些涉及酒精的。我们在Medline(通过PubMed)进行了搜索,Embase,和Cochrane图书馆,涵盖从数据库开始到2022年12月的报告。我们使用以下工具来评估偏倚风险:Cochrane偏倚风险工具的第2版,用于平行试验,用于交叉研究的Cochrane偏差风险工具,以及用于前后研究的NIH质量评估工具。我们对每种喹诺酮进行定量分析,如果有两个或更多具有指定和可比研究设计的食物效应研究可用。如果荟萃分析不适用,我们对结果进行了定性总结。
结果:我们纳入了来自101例报告的109项研究。对12种抗生素进行Meta分析,其余药物采用定性合成。在研究中,60.5%是开放标签,cross-over,根据FDA的建议。我们判断46%的研究具有高偏倚风险,只有4%的研究具有低偏倚风险。在19种具有食物影响数据的喹诺酮类药物中,14人(74%)有潜在的临床重要相互作用。对于萘啶酸,二甲氧苄酸,和托舒沙星,食物对生物利用度产生了很高的积极影响(AUC或Cmax增加了>45%),然而,剩下的药物,餐后吸收较低。食物最显著的负面影响(AUC或Cmax下降>40%)发生在德拉沙星胶囊和诺氟沙星,而中度影响(AUC或Cmax降低30-40%)发生在奈莫沙星和鲁氟沙星。当与抗酸剂和矿物质补充剂共同给药时,所有14种分析的喹诺酮类药物的生物利用度都大大降低。除了钙制剂。评估了10种喹诺酮类药物对饮料的影响,在牛奶存在下,50%的吸收显着降低(环丙沙星的负面影响最高)。此外,当与橙汁一起食用时,环丙沙星和左氧氟沙星都表现出生物利用度受损,特别是钙强化的。
结论:几个因素可能会影响相互作用,包括喹诺酮类药物的物理化学特征,干预的类型,药物制剂,以及病人的健康状况。由于纳入研究的现状较差,我们评估的证据质量较低,他们的方法多样性,以及个别药物的数据可用性不均衡。
OBJECTIVE: Managing drug-food interactions is essential for optimizing the effectiveness and safety profile of quinolones. Following PRISMA guidelines, we systematically reviewed the influence of dietary interventions on the bioavailability of 22 quinolones.
METHODS: All studies describing or investigating the impact of food, beverages,
antacids, and mineral supplements on pharmacokinetic parameters or pharmacokinetic/pharmacodynamic indices of orally taken quinolones were considered for inclusion. We excluded reviews, in vitro and in silico studies, studies performed on animals, and those involving alcohol. We performed the search in Medline (via PubMed), Embase, and Cochrane Library, covering reports from database inception to December 2022. We used the following tools to assess the risk of bias: version 2 of the Cochrane risk-of-bias tool for parallel trials, the Cochrane risk-of-bias tool for cross-over studies, and the NIH quality assessment tool for before-after studies. We performed quantitative analyses for each quinolone if two or more food-effect studies with specified and comparable study designs were available. If meta-analyses were not applicable, we qualitatively summarized the results.
RESULTS: We included 109 studies from 101 reports. Meta-analyses were conducted for 12 antibiotics and qualitative synthesis was employed for the remaining drugs. Of the studies, 60.5% were open-label, cross-over, as recommended by FDA. We judged 46% of studies as having a high risk of bias and only 4% of having a low risk of bias. Among 19 quinolones with available food impact data, 14 (74%) had potentially clinically important interactions. For nalidixic acid, oxolinic acid, and tosufloxacin, food exerted a high positive impact on bioavailability (AUC or Cmax increased by > 45%), whereas, for all the remaining drugs, postprandial absorption was lower. The most significant negative influence of food (AUC or Cmax decreased by > 40%) occurred for delafloxacin capsules and norfloxacin, whereas the moderate influence (AUC or Cmax decreased by 30-40%) occurred for nemonoxacin and rufloxacin. All 14 analysed quinolones showed a substantial reduction in bioavailability when co-administered with
antacids and mineral supplements, except for calcium preparations. The impact of beverages was evaluated for 10 quinolones, with 50% experiencing significantly reduced absorption in the presence of milk (the highest negative impact for ciprofloxacin). Moreover, both ciprofloxacin and levofloxacin demonstrated compromised bioavailability when consumed with orange juice, particularly calcium-fortified.
CONCLUSIONS: Several factors may influence interactions, including the physicochemical characteristics of quinolones, the type of intervention, drug formulation, and the patient\'s health status. We assessed the quality of evidence as low due to the poor actuality of included studies, their methodological diversity, and uneven data availability for individual drugs.