沙丁胺醇对左氧氟沙星在大鼠血浆和肺中的处置动力学的影响

IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Current drug metabolism Pub Date : 2024-01-01 DOI:10.2174/0113892002314136240816094609
Murat Ali Cicekler, Halis Oguz, Orhan Corum
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引用次数: 0

摘要

背景:抗生素和支气管扩张药物可同时用于细菌感染引起的呼吸困难。左氧氟沙星(LVX)和沙丁胺醇(SLB)可同时用于呼吸困难。然而,目前还没有研究表明同时使用沙丁胺醇会如何影响大鼠体内左氧氟沙星的药代动力学:本研究旨在探讨 SLB 对大鼠血浆和肺部 LVX 药代动力学的影响:方法:将 132 只大鼠随机分为两组:方法:将 132 只大鼠随机分为两组:LVX 组(n=66)和 LVX+SLB 组(n=66)。腹腔注射 LVX 和口服 SLB 的剂量分别为 50 毫克/千克和 3 毫克/千克。利用高效液相色谱法和紫外线测定血浆和肺中的 LVX 浓度。药代动力学参数通过非室分析法进行评估:血浆中 LVX 的 0 至 16 h 曲线下面积(AUC0-16)、终末消除半衰期、分布容积、总清除率和峰值浓度分别为 42.57 h*μg/mL、2.32 h、3.91 L/kg、1.17 L/h/kg 和 23.96 μg/mL。与 SLB 同时给药时,LVX 的血浆和肺部药代动力学参数没有发生变化。单独给药和与 SLB 联合给药后,LVX 的 AUC0-16 肺/AUC0-16 血浆比分别为 1.60 和 1.39:结论:肺组织中的 LVX 浓度高于血浆中的浓度。结论:肺组织中的 LVX 浓度高于血浆中的浓度。给大鼠服用 SLB 不会影响 LVX 的血浆和肺药代动力学以及肺渗透比。有必要揭示 LVX 在多次给药和通过不同途径给药 SLB 后的药代动力学变化。
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Effect of Salbutamol on the Disposition Kinetics of Levofloxacin in the Plasma and Lung of Rats.

Background: Antibiotics and bronchodilator drugs can be used together in respiratory distress caused by bacterial infections. Levofloxacin (LVX) and Salbutamol (SLB) can be used simultaneously in respiratory distress. However, there have been no investigations on how the concurrent use of SLB can affect the pharmacokinetics of LVX in rats.

Objective: The purpose of this study was to investigate the influence of SLB on the plasma and lung pharmacokinetics of LVX in rats.

Methods: A total of 132 rats were randomly assigned to two groups: LVX (n=66) and LVX+SLB (n=66). LVX (intraperitoneal) and SLB (oral) were administered to rats at doses of 50 and 3 mg/kg, respectively. The concentrations of LVX in the plasma and lungs were determined through the utilization of high-performance liquid chromatography along with UV. Pharmacokinetic parameters were assessed by non-compartmental analysis.

Results: The area under the curve from 0 to 16 h (AUC0-16), terminal elimination half-life, volume of distribution, total body clearance, and peak concentration of LVX in the plasma were 42.57 h*μg/mL, 2.32 h, 3.91 L/kg, 1.17 L/h/kg, and 23.96 μg/mL, respectively. There were no alterations observed in the plasma and lung pharmacokinetic parameters of LVX when co-administered with SLB. The AUC0-16 lung/AUC0-16 plasma ratios of LVX were 1.60 and 1.39 after administration alone and co-administration with SLB, respectively.

Conclusion: The concentration of LVX in lung tissue was higher than that in plasma. SLB administration to rats did not affect the plasma and lung pharmacokinetics and lung penetration ratio of LVX. There is a need to reveal the change in the pharmacokinetics of LVX after multiple administration of both drugs and after administration of SLB by different routes.

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来源期刊
Current drug metabolism
Current drug metabolism 医学-生化与分子生物学
CiteScore
4.30
自引率
4.30%
发文量
81
审稿时长
4-8 weeks
期刊介绍: Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism, pharmacokinetics, and drug disposition. The journal serves as an international forum for the publication of full-length/mini review, research articles and guest edited issues in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the most important developments. The journal covers the following general topic areas: pharmaceutics, pharmacokinetics, toxicology, and most importantly drug metabolism. More specifically, in vitro and in vivo drug metabolism of phase I and phase II enzymes or metabolic pathways; drug-drug interactions and enzyme kinetics; pharmacokinetics, pharmacokinetic-pharmacodynamic modeling, and toxicokinetics; interspecies differences in metabolism or pharmacokinetics, species scaling and extrapolations; drug transporters; target organ toxicity and interindividual variability in drug exposure-response; extrahepatic metabolism; bioactivation, reactive metabolites, and developments for the identification of drug metabolites. Preclinical and clinical reviews describing the drug metabolism and pharmacokinetics of marketed drugs or drug classes.
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