Personalized therapeutics for levofloxacin: a focus on pharmacokinetic concerns.
Personalized therapeutics for levofloxacin: a focus on pharmacokinetic concerns.
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左氧氟沙星的个性化治疗：关注药代动力学问题
DOI：
10.2147/tcrm.s59079
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发表时间：
2014
影响因子：
2.8
通讯作者：
Zhou Q
中科院分区：
文献类型：
--
作者：
Gao CH;Yu LS;Zeng S;Huang YW;Zhou Q
背景 应鼓励个性化医疗，因为患者是复杂的，这种复杂性是由生物学、医学（例如人口统计、遗传学、多药治疗和多种疾病）、社会经济和文化因素造成的。左氧氟沙星 (LVX) 是一种广谱氟喹诺酮类抗生素。在临床实践中，对 LVX 个性化治疗的认识似乎很差，这也反映在处方模式中。药代动力学-药效学研究引起了人们对使用 LVX 治疗某些革兰氏阴性感染的患者结果不佳的担忧。与此同时，LVX 疗法的新发现近年来才被零星报道。因此，有必要对个性化 LVX 治疗进行更新审查，重点关注药代动力学问题。方法 通过进行涵盖 1993 年 1 月至 2013 年 12 月期间的 PubMed 检索来确定相关文献。我们纳入了描述剂量调整和决定 LVX 药代动力学因素的研究，或探讨如何最好地预防 LVX 耐药性出现的药代动力学-药效学研究。每一篇纳入文章的全文都经过严格审查，并进行了数据解释。结果 除了限制氟喹诺酮类药物的使用外，减少药敏试验断点、选择每日一次的高剂量短程 LVX 方案以及针对特殊患者群体调整 LVX 剂量等措施有助于实现经过验证的药代动力学-药效学目标，并对抗日益增加的 LVX 耐药性。肾功能正常的肥胖个体比正常体重个体更有效地清除 LVX。与健康受试者的情况相比，钙制剂和口服 LVX 的标准 2 小时间隔不足以防止囊性纤维化患者中的螯合相互作用。性别对LVX药代动力学影响的研究得出了不一致的结论，这可能与样本量和给药途径有关。 5 岁以下儿童清除 LVX 的速度几乎是成人的两倍。接受 LVX 治疗的重症监护患者与健康受试者相比表现出显着的药代动力学差异。肌酐清除率解释了 LVX 血浆清除率的大部分群体差异。将 LVX 从静脉注射转为口服给药具有经济效益。在 LVX 方案中加入坦索罗辛对细菌性前列腺炎患者有益，因为坦索罗辛可以增加前列腺组织中 LVX 的最大浓度。应避免同时服用含多价阳离子的药物和 LVX。对于同时接受华法林和 LVX 治疗的患者，需要谨慎对待国际标准化比率的潜在变化；然而，没有必要为了避免与华法林的药物相互作用而寻求 LVX 的替代品。与 LVX 合用时，无需主动减少环孢素或他克莫司的剂量。诸如有机阴离子转运多肽1A2、P-糖蛋白、人有机阳离子转运蛋白1以及多药物和毒素挤出蛋白1等转运蛋白参与LVX的药代动力学。结论 为了提高安全性、临床成功和避免耐药性，个性化 LVX 治疗是必要的。关于特殊患者群体中 LVX 个体剂量和体内主动转运机制的新发现正在为临床实践开辟新视野。
Background Personalized medicine should be encouraged because patients are complex, and this complexity results from biological, medical (eg, demographics, genetics, polypharmacy, and multimorbidities), socioeconomic, and cultural factors. Levofloxacin (LVX) is a broad-spectrum fluoroquinolone antibiotic. Awareness of personalized therapeutics for LVX seems to be poor in clinical practice, and is reflected in prescribing patterns. Pharmacokinetic–pharmacodynamic studies have raised concerns about suboptimal patient outcomes with the use of LVX for some Gram-negative infections. Meanwhile, new findings in LVX therapeutics have only been sporadically reported in recent years. Therefore, an updated review on personalized LVX treatment with a focus on pharmacokinetic concerns is necessary. Methods Relevant literature was identified by performing a PubMed search covering the period from January 1993 to December 2013. We included studies describing dosage adjustment and factors determining LVX pharmacokinetics, or pharmacokinetic–pharmacodynamic studies exploring how best to prevent the emergence of resistance to LVX. The full text of each included article was critically reviewed, and data interpretation was performed. Results In addition to limiting the use of fluoroquinolones, measures such as reducing the breakpoints for antimicrobial susceptibility testing, choice of high-dose short-course of once-daily LVX regimen, and tailoring LVX dose in special patient populations help to achieve the validated pharmacokinetic–pharmacodynamic target and combat the increasing LVX resistance. Obese individuals with normal renal function cleared LVX more efficiently than normal-weight individuals. Compared with the scenario in healthy subjects, standard 2-hour spacing of calcium formulations and oral LVX was insufficient to prevent a chelation interaction in cystic fibrosis patients. Inconsistent conclusions were derived from studies of the influence of sex on the pharmacokinetics of LVX, which might be associated with sample size and administration route. Children younger than 5 years cleared LVX nearly twice as fast as adults. Patients in intensive care receiving LVX therapy showed significant pharmacokinetic differences compared with healthy subjects. Creatinine clearance explained most of the population variance in the plasma clearance of LVX. Switching from intravenous to oral delivery of LVX had economic benefits. Addition of tamsulosin to the LVX regimen was beneficial for patients with bacterial prostatitis because tamsulosin could increase the maximal concentration of LVX in prostatic tissue. Coadministration of multivalent cation-containing drugs and LVX should be avoided. For patients receiving warfarin and LVX concomitantly, caution is needed regarding potential changes in the international normalized ratio; however, it is unnecessary to seek alternatives to LVX for the sake of avoiding drug interaction with warfarin. It is unnecessary to proactively reduce the dose of cyclosporin or tacrolimus when comedicated with LVX. Transporters such as organic anion-transporting polypeptide 1A2, P-glycoprotein, human organic cation transporter 1, and multidrug and toxin extrusion protein 1 are involved in the pharmacokinetics of LVX. Conclusion Personalized LVX therapeutics are necessary for the sake of better safety, clinical success, and avoidance of resistance. New findings regarding individual dosing of LVX in special patient populations and active transport mechanisms in vivo are opening up new horizons in clinical practice.