Comparative diffusion of drugs through bronchial tissue

Zyl, Johann M. van; Derendinger, Brigitta; Seifart, H. I.; Bijl, Pieter van der

doi:10.1016/j.ijpharm.2008.01.028

Cited by 17 publications

(17 citation statements)

References 18 publications

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“…Between 15 and 120min higher fractions of ipratropium bromide were released into plasma as compared to fenoterol which might be due to the relative higher lipophilicity of fenoterol (log P=1.36 [20]) compared to ipratropium (log P=0.89 [20]). A lately reported continuous flow-through diffusion system for bronchial tissue also investigated the diffusion behaviour of ipratropium bromide and the  2 -agonist salbutamol [15]. The flux of ipratropium bromide across bronchial tissue was always slightly above the flux of salbutamol and both drugs reached a steady state flux rate after approximately 14 h. Since salbutamol and fenoterol are structurally related the slightly higher permeability of the  2 -agonist compared to the anticholinergic drug appears to be consistent with our observations.…”

Section: Discussionsupporting

confidence: 88%

“…The flux of ipratropium bromide across bronchial tissue was always slightly above the flux of salbutamol and both drugs reached a steady state flux rate after approximately 14 h. Since salbutamol and fenoterol are structurally related the slightly higher permeability of the  2 -agonist compared to the anticholinergic drug appears to be consistent with our observations. There were some distinct differences between our dynamic dialysis system and the flow-through diffusion model of van Zyl et al [15]. Besides the fact that they used porcine lungs their bronchial tissue area was roughly 4000fold smaller compared to ours (0.039cm 2 versus 15.9cm 2 ), the flow rate was approximately 15fold lower (1.5ml/h versus 22.8ml/h), and the drug concentration in the donor chamber was higher with 1mg/mL compared to our 0.013mg/mL (fenoterol) and 0.008mg/mL (ipratropium bromide).…”

Section: Discussionmentioning

confidence: 90%

“…for studying the role of absorption enhancers and for analysis of drug bioavailability or bioequivalence studies [13]. Recently, a continuous flow-through diffusion system for bronchial tissue has been described [15]. Typically, in these model systems tissue sections with external diameters between 4 and 10 mm are mounted on flow-through cells.…”

Section: Discussionmentioning

confidence: 99%

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Analysis of Fenoterol and Ipratropium Transfer from Human Lung Tissue into Human Plasma Using a Dynamic Dialysis Model

Trammer¹

2014

BJPR

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Aims:The aim of the current study was to establish a simple and yet as much as possible physiologic approach for a simulation of the pulmonary absorption process to compare different inhaled drugs or drug formulations. Methodology: We designed a dialysis setting that allowed monitoring the drug release from human lung tissue into a continuous-flow plasma compartment. For proof-of-concept experiments we chose the glucocorticoid fluticasone propionate (FP) as model compound. For subsequent experiments we selected a commercially available metered dose inhaler delivering a fixed combination of the short-acting ß 2 -agonist fenoterol and the muscarinic antagonist ipratropium bromide. Results: With the novel dynamic dialysis model we observed high drug transport rates from the lung tissue into plasma including an elimination phase. The concentration profile in the plasma compartment of our model system was similar to the plasma concentration courses after inhalation of FP. Compared to FP significantly higher drug fractions of Original Research ArticleBritish Journal of Pharmaceutical Research, 4(11): 1287Research, 4(11): -1299Research, 4(11): , 2014 1288 fenoterol and ipratropium bromide were released into plasma and the transfer of ipratropium was more pronounced compared to fenoterol. Again, concentration profiles in plasma were alike to those described in clinical studies. Conclusion:We suggest that this model is appropriate for rapid assessment of comparative diffusion behaviour of drugs or drug formulations from lung tissue into plasma.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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Analysis of Fenoterol and Ipratropium Transfer from Human Lung Tissue into Human Plasma Using a Dynamic Dialysis Model

Trammer¹

2014

BJPR

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“…As a hydrated salt crystalline powder, it is freely soluble in water and lower alcohol, but insoluble in lipophilic solvents, such as ether, chloroform, and fluorocarbons. It is a highly hydrophilic drug (log P = −2.21) 21. A 1% aqueous solution of IPB has a pH of 5–7.5 22.…”

Section: Introductionmentioning

confidence: 99%

Dry Powder Aerosols Generated by Standardized Entrainment Tubes From Drug Blends With Lactose Monohydrate: 2. Ipratropium Bromide Monohydrate and Fluticasone Propionate

Mansour

Mulder³

et al. 2010

Journal of Pharmaceutical Sciences

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“…For example, we assume that the alveolar tissue environment is currently homogenous and isotropic, whereas in fact the various alveoli of the lung can be quite heterogeneous with physical and chemical anisotropies that may constrain the directions of cell movement (15,23). A related assumption is that cytokines and other chemical signals diffuse at the same linear rate through the environment at each time step.…”

Section: L388mentioning

confidence: 99%

A computational model of unresolved allergic inflammation in chronic asthma

Pothen

Poynter

Bates

2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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We have previously developed an agent-based computational model to demonstrate the feasibility of a novel hypothesis we term the inflammatory twitch. This hypothesis potentially explains the dynamics of the normal response to allergic inflammation in the lung (Pothen JJ, Poynter ME, Bates JH. J Immunol 190: 3510-3516, 2013) on the basis that antigenic stimulation sets in motion both the onset of inflammation and its subsequent resolution. The result is a self-limited inflammatory event that is similar in a formal sense to a skeletal muscle twitch. We hypothesize here that the chronic airway inflammation characteristic of asthma may represent the failure of the inflammatory twitch to resolve back to baseline. Our model provides a platform with which to perform virtual experiments aimed at investigating possible mechanisms leading to accentuation and/or prolongation of the inflammatory twitch. We used our model to determine how the inflammatory twitch is modified by knocking out certain cell types, interfering with cell activity, and altering cell lifetimes. Increasing the duration of activation of proinflammatory cells (considered to be chiefly neutrophils and eosinophils) markedly accentuated and prolonged the inflammatory twitch. This aberrant twitch behavior was largely abrogated by knocking out T-helper cells (simulating the effect of corticosteroids). The aberrant inflammatory twitch was also normalized by reducing the lifetime of the proinflammatory cells, suggesting that increasing apoptosis of these cells may be a therapeutic target in asthma.

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Comparative diffusion of drugs through bronchial tissue

Cited by 17 publications

References 18 publications

Analysis of Fenoterol and Ipratropium Transfer from Human Lung Tissue into Human Plasma Using a Dynamic Dialysis Model

Analysis of Fenoterol and Ipratropium Transfer from Human Lung Tissue into Human Plasma Using a Dynamic Dialysis Model

Dry Powder Aerosols Generated by Standardized Entrainment Tubes From Drug Blends With Lactose Monohydrate: 2. Ipratropium Bromide Monohydrate and Fluticasone Propionate

A computational model of unresolved allergic inflammation in chronic asthma

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