Intrapulmonary concentration of levofloxacin in patients with idiopathic pulmonary fibrosis

Huang, Hui; Wang, Yanxun; Jiang, Chunguo; Lang, Liwei; Wang, Hongyun; Chen, Yong; Zhao, Yang; Xu, Zuojun

doi:10.1016/j.pupt.2013.10.004

Cited by 10 publications

(6 citation statements)

References 28 publications

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“…Older studies report ELF to plasma concentration ratios ranging from 1.59 to 2.69 based on AUC [1]. Since then, two studies comparing intrapulmonary concentrations of levofloxacin have been published, one study evaluating patients with idiopathic pulmonary fibrosis and one study evaluating patients with acute exacerbation of chronic bronchitis [70,71]. Huang and colleagues compared plasma and ELF concentrations of 10 patients with idiopathic pulmonary fibrosis with 10 patients in a control group following a single oral dose of levofloxacin 500 mg [70].…”

Section: Levofloxacinmentioning

confidence: 99%

“…Since then, two studies comparing intrapulmonary concentrations of levofloxacin have been published, one study evaluating patients with idiopathic pulmonary fibrosis and one study evaluating patients with acute exacerbation of chronic bronchitis [70,71]. Huang and colleagues compared plasma and ELF concentrations of 10 patients with idiopathic pulmonary fibrosis with 10 patients in a control group following a single oral dose of levofloxacin 500 mg [70]. The mean ELF concentration was 10.17 µg/mL in the idiopathic pulmonary fibrosis group and 27.81 µg/mL in the control group.…”

Section: Levofloxacinmentioning

confidence: 99%

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Penetration of Antibacterial Agents into Pulmonary Epithelial Lining Fluid: An Update

Drwiega

Rodvold

2021

Clin Pharmacokinet

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A comprehensive review of drug penetration into pulmonary epithelial lining fluid (ELF) was previously published in 2011. Since then, an extensive number of studies comparing plasma and ELF concentrations of antibacterial agents have been published and are summarized in this review. The majority of the studies included in this review determined ELF concentrations of antibacterial agents using bronchoscopy and bronchoalveolar lavage, and this review focuses on intrapulmonary penetration ratios determined with area under the concentration-time curve from healthy human adult studies or pharmacokinetic modeling of various antibacterial agents. If available, pharmacokinetic/pharmacodynamic parameters determined from preclinical murine infection models that evaluated ELF concentrations are also provided. There are also a limited number of recently published investigations of intrapulmonary penetration in critically ill patients with lower respiratory tract infections, where greater variability in ELF concentrations may exist. The significance of these changes may impact the intrapulmonary penetration in the setting of infection, and further studies relating ELF concentrations to clinical response are needed. Phase I drug development programs now include assessment of initial pharmacodynamic target values for pertinent organisms in animal models, followed by evaluation of antibacterial penetration into the human lung to assist in dosage selection for clinical trials in infected patients. The recent focus has been on β-lactam agents, including those in combination with β-lactamase inhibitors, particularly due to the rise of multidrug-resistant infections. This manifests as a large portion of the review focusing on cephalosporins and carbapenems, with or without β-lactamase inhibitors, in both healthy adult subjects and critically ill patients with lower respiratory tract infections. Further studies are warranted in critically ill patients with lower respiratory tract infections to evaluate the relationship between intrapulmonary penetration and clinical and microbiological outcomes. Our clinical research experience with these studies, along with this literature review, has allowed us to outline key steps in developing and evaluating dosage regimens to treat extracellular bacteria in lower respiratory tract infections.

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Section: Levofloxacinmentioning

confidence: 99%

Section: Levofloxacinmentioning

confidence: 99%

Penetration of Antibacterial Agents into Pulmonary Epithelial Lining Fluid: An Update

Drwiega

Rodvold

2021

Clin Pharmacokinet

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“…However, the AUC 0 -24 ratios in the pulmonary fibrosis group were lower than those in the normal group. In a preliminary clinical study, Huang et al compared the difference in intrapulmonary concentration of levofloxacin between patients with normal lung function and patients with IPF (15). Though they did not compare the ELF/plasma concentration ratios between the two groups, they found that the mean ELF concentration at 3 h in IPF patients (n ϭ 10) was 50% lower than that in patients with normal lung function (n ϭ 10) (15).…”

Section: Discussionmentioning

confidence: 99%

Penetration of Ciprofloxacin and Amikacin into the Alveolar Epithelial Lining Fluid of Rats with Pulmonary Fibrosis

Yang

Mei

et al. 2017

Antimicrob Agents Chemother

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We determined the concentration-time profiles of ciprofloxacin and amikacin in serum and alveolar epithelial lining fluid (ELF) of rats with or without pulmonary fibrosis and investigated the effect of pulmonary fibrosis on the capacity for penetration of antimicrobials into the ELF of rats. Pulmonary fibrosis was induced in rats with a single intratracheal instillation of bleomycin. After intravenous injection of ciprofloxacin or amikacin, blood and bronchoalveolar lavage fluid samples were collected. Urea concentrations in serum and lavage fluid were determined using an enzymatic assay. Ciprofloxacin and amikacin concentrations were determined by high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry, respectively. The mean ratio of ELF to plasma concentrations of ciprofloxacin at each time point in the normal group did not significantly differ from that in the pulmonary fibrosis group. However, the ratio of the ciprofloxacin area under the concentration-time curve from 0 to 24 h (AUC) in ELF to the AUC in plasma was 1.02 in the normal group and 0.76 in the pulmonary fibrosis group. The mean ELF-to-plasma concentration ratios of amikacin at each time point in the normal group were higher than those in the pulmonary fibrosis group, reaching a statistically significant difference at 1, 2, and 4 h. The ratio of the AUC in ELF to the AUC in plasma was 0.49 in the normal group and 0.27 in the pulmonary fibrosis group. In conclusion, pulmonary fibrosis can influence the penetration of antimicrobials into the ELF of rats and may have a marked effect on the penetration of amikacin than that of ciprofloxacin.

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“…Stopień penetracji antybiotyków do błony śluzowej oskrzeli i miąższu płucnego jest bardzo zróżnicowany i zależny od toczącego się procesu zapalnego [32,33]. Ponadto antybiotyki wykazujące wysoką kumulację wewnątrzko-mórkową in vitro osiągają także wysokie stężenia w błonie śluzowej oskrzeli oraz w miąższu płucnym i dlatego wyróż-niono grupę antybiotyków hydrofilnych, do których nale-żą beta-laktamy i aminoglikozydy (które osiągają w płynach zewnątrzkomórkowych płuc takie samo stężenie jak w surowicy) oraz grupę antybiotyków lipofilnych, do których zaliczono: fluorochinolony, tetracykliny i makrolidy (osiągające wyższe stężenia w tkankach niż w surowicy) [33][34][35].…”

Section: Charakterystyka Lewofloksacynyunclassified

Lewofloksacyna i moksyfloksacyna w leczeniu zakażeń bakteryjnych

Płusa¹

2016

Forum Zakażeń

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STRESZCZENIE: Klasyfikacja fluorochinolonów została oparta na spektrum mikrobiologicznym i cechach farmakokinetycznych kolejno wprowadzanych preparatów, które charakteryzowały się lepszymi właściwościami farmakodynamicznymi, w tym znaczną penetracją do wnę-trza makrofagów i miejsca toczącego się procesu zapalnego. Przeprowadzona porównaw-cza analiza lewofloksacyny i moksyfloksacyny wskazuje na ich skuteczność kliniczną w kontrolowaniu zakażeń układowych zarówno w obrębie układu oddechowego, jak i moczowego, zwłaszcza w przypadku lewofloksacyny. Z tego powodu obydwa preparaty znalazły się w obowiązujących obecnie rekomendacjach postępowania w zakażeniach. Narastająca oporność na antybiotyki zmusza do ich racjonalnego stosowania -zgodnego ze światowymi wytycznymi.SŁOWA KLUCZOWE: lewofloksacyna, moksyfloksacyna, zakażenie ABSTRACT: Classification of fluoroquinolones is based on the spectrum of microbiological and pharmacokinetic characteristics in turn introduced preparations, which were characterized by improved pharmacodynamic properties, including significant penetration into the macrophages and inflammatory tissue. Conducted a comparative analysis of levofloxacin and moxifloxacin indicates clinically effective in controlling systemic infections both within the respiratory tract and urinary tract, particularly levofloxacin. For this reason, two products had been included in the recommendations of conduct infections developed in recent years. Increasing antibiotic resistance forces to their rational use -in accordance with international guidelines. WSTĘP Wskazaniem do stosowania antybiotyków są stany zapalne wywołane przez drobnoustroje. W zależności od rodzaju patogenu, jego aktywności i wrażliwości na podawany preparat o działaniu hamującym rozwój lub zabijającym bakterie, uzyskuje się odpowiedni efekt kliniczny. Najważniej-szym elementem tego postępowania, poza charakterystyką patogenu, są cechy farmakokinetyczne stosowanego antybiotyku, w tym: jego spektrum działania, stopień penetracji do miejsca toczącego się procesu zapalnego, wykazywane interakcje z innymi cząsteczkami oraz bezpieczeństwo dla chorego [1]. Posiadana wiedza w tym zakresie jest bardzo pomocna przy podejmowaniu decyzji terapeutycznych. KLASYFIKACJA FLUOROCHINOLONÓWChinolony należą do czynników przeciwbakteryjnych zsyntetyzowanych w latach 60. XX wieku w wyniku modyfikacji podstawowej dwupierścieniowej chemicznej struktury. Współczesna klasyfikacja fluorochinolonów jest oparta na spektrum mikrobiologicznym i cechach farmakokinetycznych poszczególnych preparatów. Należy podkreślić, Artyku jest dost pny na zasadzie dozwolonego u ytku osobistego. Dalsze rozpowszechnianie (w tym umieszczanie w sieci) jest zabronione i stanowi powa ne naruszenie przepisów prawa autorskiego oraz grozi sankcjami prawnymi.

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Intrapulmonary concentration of levofloxacin in patients with idiopathic pulmonary fibrosis

Cited by 10 publications

References 28 publications

Penetration of Antibacterial Agents into Pulmonary Epithelial Lining Fluid: An Update

Penetration of Antibacterial Agents into Pulmonary Epithelial Lining Fluid: An Update

Penetration of Ciprofloxacin and Amikacin into the Alveolar Epithelial Lining Fluid of Rats with Pulmonary Fibrosis

Lewofloksacyna i moksyfloksacyna w leczeniu zakażeń bakteryjnych

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