Relationship between Trough Plasma and Epithelial Lining Fluid Concentrations of Voriconazole in Lung Transplant Recipients

Heng, Siow Chin; Snell, Gregory I; Levvey, Bronwyn; Keating, D.; Westall, Glen P.; Williams, Trevor; Whitford, Helen; Nation, Roger L.; Slavin, Monica A; Morrissey, Orla; Kong, David Chee Ming

doi:10.1128/aac.00942-13

Cited by 15 publications

(12 citation statements)

References 17 publications

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“…Of these 21 studies, 9 were conducted in Asia, 11 , 12 , 14 , 29 , 30 , 39 , 41 – 43 4 included only patients diagnosed with proven or probable IFI 12 , 19 , 20 , 29 and 6 included patients with concomitant use of other antifungals. 9 , 19 , 20 , 31 , 35 , 42 Five studies used voriconazole for prophylaxis 34 , 36 , 40 , 41 , 44 and 16 used voriconazole for treatment. 9 – 12 , 14 , 19 , 20 , 29 – 31 , 35 , 37 – 39 , 42 , 43 Two studies were conducted in children, one used voriconazole for treatment 35 and the other for prophylaxis.…”

Section: Resultsmentioning

confidence: 99%

Trough concentration of voriconazole and its relationship with efficacy and safety: a systematic review and meta-analysis

Jin

Wang

Falcione

et al. 2016

J. Antimicrob. Chemother.

131

139

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Section: Resultsmentioning

confidence: 99%

Trough concentration of voriconazole and its relationship with efficacy and safety: a systematic review and meta-analysis

Jin

Wang

Falcione

et al. 2016

J. Antimicrob. Chemother.

131

139

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“…However, as macrolide drugs may accumulate in respiratory organs, the concentrations of macrolides at the infection site were undoubtedly better to predict the clinical outcome. Although several intrapulmonary pharmacokinetic studies have been conducted using BAL in humans ( Conte et al, 2000a , b , 2005 ; Heng et al, 2013 ), the BAL technique was still only limitedly applied to establish intrapulmonary pharmacokinetic models among mammal animals ( Womble et al, 2007 ; Villarino et al, 2013 ). Those intrapulmonary pharmacokinetics experiments using BAL technique were normally designed for long term studies with long sampling intervals.…”

Section: Discussionmentioning

confidence: 99%

The Epidemiologic and Pharmacodynamic Cutoff Values of Tilmicosin against Haemophilus parasuis

Zhang

Hao

et al. 2016

Front. Microbiol.

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The aim of this study was to establish antimicrobial susceptibility breakpoints for tilmicosin against Haemophilus parasuis, which is an important pathogen of respiratory tract infections. The minimum inhibitory concentrations (MICs) of 103 H. parasuis isolates were determined by the agar dilution method. The wild type (WT) distribution and epidemiologic cutoff value (ECV) were evaluated by statistical analysis. The new bronchoaveolar lavage was used to establish intrapulmonary pharmacokinetic (PK) model in swine. The pharmacokinetic (PK) parameters of tilmicosin, both in pulmonary epithelial lining fluid (PELF) and in plasma, were determined using high performance liquid chromatography method and WinNonlin software. The pharmacodynamic cutoff (COPD) was calculated using Monte Carlo simulation. Our results showed that 100% of WT isolates were covered when the ECV was set at 16 μg/mL. The tilmicosin had concentration-dependent activity against H. parasuis. The PK data indicated that tilmicosin concentrations in PELF was rapidly increased to high levels at 4 h and kept stable until 48 h after drug administration, while the tilmicosin concentration in plasma reached maximum levels at 4 h and continued to decrease during 4–72 h. Using Monte Carlo simulation, COPD was defined as 1 μg/mL. Conclusively, the ECV and COPD of tilmicosin against H. parasuis were established for the first time based on the MIC distribution and PK-PD analysis in the target tissue, respectively. These values are of great importance for detection of tilmicosin-resistant H. parasuis and for effective treatment of clinical intrapulmonary infection caused by H. parasuis.

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“…Concentrations of antifungal agents within the ELF are useful for prophylaxis and the treatment of early stages of IPA, but are probably of little relevance for the later stages of disease . Clinically, the volume of ELF recovered in the bronchoalveolar lavage aspirate , and the concentration of voriconazole in ELF can be obtained . Additionally, a large interindividual variability has been observed in the ELF concentrations of voriconazole .…”

Section: Discussionmentioning

confidence: 99%

Uptake and efflux kinetics, and intracellular activity of voriconazole against Aspergillus fumigatus in human pulmonary epithelial cells: a new application for the prophylaxis and early treatment of invasive pulmonary aspergillosis

Wang

Yang

Chen

et al. 2017

Fundamemntal Clinical Pharma

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Invasive pulmonary aspergillosis (IPA), most caused by Aspergillus fumigatus, is a serious life-threatening infection in immunocompromised patients. Voriconazole is used to prevent and treat IPA. However, little is known about the pharmacological characteristics of voriconazole in pulmonary epithelial cells, which are the target site for the prophylaxis and early treatment of IPA. The aim of the study was to evaluate the kinetics and activity of voriconazole against A. fumigatus in A549 cells. High-performance liquid chromatography/tandem mass spectrometry and time-kill method were used to study the cellular pharmacokinetic and pharmacodynamics of voriconazole. Voriconazole exerted a concentration-dependent toxic effect on A549 cells and could penetrate into cells, reaching plateau concentrations of 1.14 ± 0.64, 3.72 ± 1.38 and 6.36 ± 0.95 ng/mg protein after A549 cells were exposed to voriconazole at extracellular concentrations of 2, 8 and 16 mg/L for 2 h, respectively. The efflux of voriconazole was rapid, with a half-life of 10.2 min. Voriconazole can decrease the A. fumigatus conidia invade cells, and the number of viable A. fumigatus conidia in cells can be decreased 2.1- to 20.6-fold when A549 cells were cultured in medium containing voriconazole. After 24-h incubation, 75.6% and 80.5% of intracellular A. fumigatus were killed when extracellular voriconazole concentration was 8 and 16 mg/L, respectively. This study illustrated a new application for the prophylaxis and early treatment of IPA from the cellular pharmacokinetics and pharmacodynamics and emphasized the importance of monitoring concentrations of voriconazole in epithelial lining fluid in immunocompromised patients receiving voriconazole therapy.

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Relationship between Trough Plasma and Epithelial Lining Fluid Concentrations of Voriconazole in Lung Transplant Recipients

Cited by 15 publications

References 17 publications

Trough concentration of voriconazole and its relationship with efficacy and safety: a systematic review and meta-analysis

Trough concentration of voriconazole and its relationship with efficacy and safety: a systematic review and meta-analysis

The Epidemiologic and Pharmacodynamic Cutoff Values of Tilmicosin against Haemophilus parasuis

Uptake and efflux kinetics, and intracellular activity of voriconazole against Aspergillus fumigatus in human pulmonary epithelial cells: a new application for the prophylaxis and early treatment of invasive pulmonary aspergillosis

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