Steady-State Intrapulmonary Concentrations of Moxifloxacin, Levofloxacin, and Azithromycin in Older Adults

Capitano, Blair; Mattoes, Holly M.; Shore, Eric; O’Brien, Aidan; Braman, Sidney S.; Sutherland, Christina A.; Nicolau, David P.

doi:10.1378/chest.125.3.965

Cited by 112 publications

(91 citation statements)

References 22 publications

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“…13,29,42 Previous studies have consistently reported significantly higher concentrations in ELF and AM than in plasma throughout the therapy course, with concentrations in AM always far higher than ELF. Rapid distribution of macrolides into the lung compartments had resulted in lower plasma concentrations throughout dosing interval, 13,29,42 thus leading to theoretical concerns of its use in primary bacteremia. In healthy adults administered standard doses of azithromycin, at the end of 24-hour dosing interval, 100% ELF concentrations (n = 4) were above the susceptibility breakpoint of 1 mg/L.…”

Section: Macrolidesmentioning

confidence: 92%

“…10 The ELF to plasma ratio (ratio of the area under the concentration time curve (AUC) of antibiotic for 1 dosing interval in ELF:plasma) of fluoroquinolones is reported to be >100% when administered by either the oral or intravenous (IV) route. [11][12][13] Numerous studies have reported the extensive penetration of fluoroquinolones into the lung tissue (eg, AM) 13,14 with concentrations that were higher than those in plasma and ELF. Similarly with tigecycline and oxazolidinones, the ELF to plasma penetration is also high.…”

Section: Physicochemical Propertiesmentioning

confidence: 99%

“…Importantly, dose adjustment should be considered necessary in renal dysfunction or in the elderly, as these patients will have a reduced clearance of levofloxacin. 12,13 With the excellent penetration into the lung tissue, use of fluoroquinolones in lung infections is usually reliable as long as pathogen susceptibility remains acceptable. Higher dosing regimens will be of course necessary when aiming for a more aggressive PK/PD targets.…”

Section: Fluoroquinolonesmentioning

confidence: 99%

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Defining Antibiotic Dosing in Lung Infections

Jamal

Abdul‐Aziz

Lipman

et al. 2013

Clinical Pulmonary Medicine

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Defining optimal antibiotic dosing for treatment of lung infections is challenging because of the interrelationship between patient characteristics (eg, pathophysiological changes of lung during an infection, albumin level, renal function), antibiotic characteristics (eg, physicochemical properties, protein binding), and bacterial pathogen susceptibility. Measurement of antibiotic concentration in the lung compartments, such as epithelial lining fluid (ELF), is important to describe the drug exposure at site of infection. This article reviews published data on antibiotic penetration described by the ELF to plasma (ELF:plasma) ratios and the probability of pharmacokinetic/ pharmacodynamics (PK/PD) attainment at the target site with current dosing regimens to outline dosing strategies that could optimize the PK/PD indices. Antibiotic physicochemical properties could be used to predict the extent of penetration into the lung tissues. Lipophilic antibiotics penetrate well into the lung compartments; however, standard dosing regimens generally seem to be insufficient to achieve optimal PK/PD indices in the ELF, particularly during severe infections. Aggressive dosing regimens are required for antibiotics that poorly or moderately penetrate the lung tissues, whereas nebulization could be the alternative method to enhance antibiotic concentration at the target site. Special populations such as the critically ill, patients on renal replacement therapy, and those with renal impairment need dosing to be individualized, as these populations have high PK variability. Dosing based on free drug concentrations should be considered preferred, as these concentrations frequently reflect the antibiotic concentration at the target site. Therefore, the use of therapeutic drug monitoring should be considered necessary, whenever possible, to guide dosing in lung infection.

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Section: Macrolidesmentioning

confidence: 92%

Section: Physicochemical Propertiesmentioning

confidence: 99%

Section: Fluoroquinolonesmentioning

confidence: 99%

See 1 more Smart Citation

Defining Antibiotic Dosing in Lung Infections

Jamal

Abdul‐Aziz

Lipman

et al. 2013

Clinical Pulmonary Medicine

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“…[16][17][18][19][20][21][22][23] The volume of ELF contained in each BALf sample was determined by the urea dilution method. Urea diffuses freely throughout the body with the concentration in plasma equal to that in other body fluids.…”

Section: Estimation Of Epithelial Lining Fluid (Elf) Volumes and Detementioning

confidence: 99%

“…Although, the effect of treatmnt on serum IgE levels on asthmatic patients heve been reported. In a study, Ohrui et al reported that 3 month treatment with 800 mg/ day of inhaled beclomethasone dipropionate led to improvement of symptoms and a significant reduction of circulating total and allergen-specific IgE levels in a group of atopic asthmatics (18). After administration of corticosteroids, the reduction of IL-4 occurs that effect on synthesis of IgE.…”

mentioning

confidence: 99%

Poster Abstracts

2008

Respirology

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Background: Total serum IgE level as a marker of allergic inflammation is associated with severity of the asthma, and is targeted for treatment of it. The aim of this study was to determine the relationship between total serum IgE levels with response to routine drug treatment in acute asthma. Materials and methods: The study was carried out in 162 subjects with acute asthma. Total IgE serum, peripheral blood cell and eosinophils counts were measured. Management in all of the patients was adjusted according to the level of asthma severity, and spirometry was performed before and 2 weeks after treatment. The relationships between baseline and percentage changes of FEV1 (forced expiratory volume in 1 second), FVC (forced vital capacity), FEF25-75% (forced expiratory flow at 25 to 75% of vital capacity), peripheral white blood cell and eosinophils counts with asthma with high IgE levels (≥100 IU/ml) to those of patients with low IgE levels (<100 IU/ml) were studied cross-sectionally. Results: No relationship between percentage changes of FEV1, FVC, FEF25-75%, white blood cell count, and peripheral blood eosinophil; with high and low level of total serum IgE was seen (p = 0.89; 0.74; 0.68; 0.72; 0.44; respectively). No significant relationships between baseline predicted of FEV1, FVC, and FEF25-75% among asthma with high and low levels of total serum IgE was observed (p = 0.79; 0.69; 0.45; respectively). Conclusion: On the basis of these findings we conclude that the level of total serum IgE levels, peripheral white blood cell counts and eosinophils percent cannot be used to predict the response to anti-asthmatic drugs. Keywords: Asthma, predicting response; therapy; total serum IgE Introduction: Asthma is a condition characterized by variability in airflow obstruction, fluctuation of symptoms, and changes in the level of bronchial responsiveness and airway inflammation. Elevated serum IgE level as a marker of allergic inflammation and atopy contribute to asthma, and is considered as a potent prediction for the development of asthma. In patients with higher IgE, had a greater increase in PC20 when administered inhaler corticosteroids than those with lower IgE levels (1). Recently Moin et al. reported that in children, higher IgE levels lower the probability of hospitalization during asthmatic attack (2). It is unknown, in asthma, whether patients who do not respond well to one medication might respond to the other medication. In children with mild-to-moderate persistent asthma, a favourable response to inhaler corticosteroid was associated with higher levels of exhaled nitric oxide, total eosinophils counts, levels of serum IgE and other markers of allergic inflammation (3). Moreover, Cai et al. in a study on patients with stable mild to moderate asthma that were treated with montelukast in four-week concluded that there was not significant correlation between the clinical response and serum IgE levels (4). The percentage of patients with asthma and airway responsiveness in general population with higher IgE levels ...

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Develop adult extrapolation to pediatrics and pediatric dose optimization based on the physiological pharmacokinetic model of azithromycin

Liang

Zhang

et al. 2023

Biopharm & Drug Disp

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Physiologically-based pharmacokinetic (PBPK) models are more frequently used for supporting pediatric dose selection in small-molecule drugs. Through literature research, drug parameters of azithromycin and clinical data from different studies were obtained. Through parameter optimization of the absorption and dissolution process, the adult intravenous model was extended to the adult oral model. The adult intravenous and oral PBPK models are precise to meet the AAFE<2 standard, and the pharmacokinetic parameters of the predicted values of the model are all within the mean standard deviation of the clinical observations. The values of plasma protein unbound fraction, renal clearance, and gastric juice pH between adults and pediatrics were changed by using the age-dependent pediatric organ maturity formula, and the adult model was extrapolated to the pediatric model. The final developed pediatric PBPK model was used to evaluate optimal dosing for children of different developmental ages. The relationship between the frist dose and age was as follows: 8.8 mg/kg/day from 0.5 to 2 years old, 9.2 mg/kg/day from 3 to 6 years old, 9.4 mg/kg/day from 7 to 12 years old, and 8.2 mg/kg/day from 13 to 18 years old, taken in half for 2-5 days. Simultaneously, the simulated exposures achieved with the dosing regimen proposed were comparable to adult plasma exposures for treatment of community-acquired pneumonia. A reasonable azithromycin pharmacokinetic-pharmacodynamic model for adults and pediatrics has been established, which can be demonstrated by the use of literature pediatric data to develop pediatric PBPK models, expanding the scope of this powerful modeling tool.

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Steady-State Intrapulmonary Concentrations of Moxifloxacin, Levofloxacin, and Azithromycin in Older Adults

Cited by 112 publications

References 22 publications

Defining Antibiotic Dosing in Lung Infections

Defining Antibiotic Dosing in Lung Infections

Poster Abstracts

Develop adult extrapolation to pediatrics and pediatric dose optimization based on the physiological pharmacokinetic model of azithromycin

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