Biomedical subjects

Laurent Vecellio

Publications and source records attributed to Laurent Vecellio.

7 recordsLinked to original sources

PubMed2007

Lung deposition of HFA beclomethasone dipropionate in an animal model of bronchopulmonary dysplasia.

The best delivery of a drug in ventilated neonates is obtained when using a small particle diameter solution administered via a spacer. Lung deposition of hydrofluoroalkane beclomethasone dipropionate (QVAR, 1.3 microm particles), delivered via an Aerochamber-MV15, was measured in piglets under conditions mimicking ventilated severely ill neonates (uncuffed 2.5 mm endotracheal tube; peak pressure 16 cm H2O; respiratory rate 40/min). After determining the mass and particle size distribution of the 99mTc-labeled and unlabeled drug, three lung deposition studies were performed: after 1 h of ventilation (controls, n = 18), after 48 h aggressive ventilation inducing an acute lung injury (nine piglets out of the controls), and after increasing the pressure to 24 cm H2O during drug delivery (five piglets out of the nine with acute lung injury). All piglets were then killed for lung histology. Results (median, range), expressed as a percentage of the delivered dose, were compared using an inferential or the Friedman test. While lung deposition was low, it was greater (p = 0.003) in controls (2.66%, 0.50-7.70) than in piglets with histologically confirmed acute lung injury (0.26%, 0.06-1.28) or under a high-pressure ventilation (1.01%, 0.30-2.15). Lung deposition of QVAR in an animal model of ventilated neonates is low, variable, and dramatically affected by lung injury.

Aerosol Propellants↗

PubMed2006

New ipratropium formulation to decrease nebulization time.

A new anticholinergic aerosol containing 0.5mg ipratropium bromide dissolved in 1mL of solution has been produced with the purpose of decreasing nebulization time for patients compared to the traditional formulation which is twice as voluminal (0.5mg/2mL, Boehringer-Ingelheim, France). The aim of this study was to compare aerosol characteristics (inhaled mass, particle size distribution and nebulization time) of these two formulations of ipratropium bromide, nebulized alone and with terbutaline (5mg/2mL, Astra Zeneca, Sweden), to determine whether the new formulation was equivalent to the old one. Four different jet nebulizers were used: PariLC+, Atomisor NL9M, Sidestream and Mistyneb. Statistical analysis of the results showed that for all types of nebulizer, the inhaled mass of ipratropium bromide 0.5mg/1mL was significantly lower than the inhaled mass of ipratropium bromide 0.5mg/2mL, and that there was no statistical difference between the inhaled mass of ipratropium bromide 0.5mg/1mL+terbutaline 5mg/2mL and the inhaled mass of ipratropium bromide 0.5mg/2mL+terbutaline 5mg/2mL. The study also showed that the new formulation of ipratropium bromide (0.5mg/1mL) mixed with terbutaline allowed a 26% decrease in nebulization time compared to the old formulation (0.5mg/2mL) mixed with terbutaline without changing aerosol characteristics (inhaled mass and particle size distribution). This leads to the conclusion that a 2mL minimum volume is required for nebulization, and that nebulization of ipratropium bromide 0.5mg/1mL alone must be avoided.

Aerosols↗

PubMed2005

Gemcitabine aerosol: in vitro antitumor activity and deposition imaging for preclinical safety assessment in baboons.

AIM: To characterize gemcitabine aerosol, its in vitro activity against lung cancer cells, its deposition, and tolerance in a non-human primate model. METHODS: In vitro cytotoxicity of nebulized gemcitabine against NCI-H460 and A549 lung cancer cells was tested using a growth inhibition assay and compared with non-nebulized gemcitabine. The (99m)Tc-DTPA-radiolabeled gemcitabine aerosol was characterized by cascade impaction and the gemcitabine mass/(99m)Tc activity relationship was established for further quantitative nuclear imaging. Nine weekly inhalations at a target dose of 1 mg/kg body weight of gemcitabine were performed in three baboons using dynamic scintigraphic acquisitions for continuous monitoring of gemcitabine delivery during inhalation. Gemcitabine plasma concentrations were measured during the first inhalation. RESULTS: Growth inhibition assays for both NCI-H460 and A549 cells did not differ between nebulized and non-nebulized gemcitabine. Aerosol characterization showed a particle mass median aerodynamic diameter of 3.7+/-0.8 microm and a linear relationship between gemcitabine mass (y) and (99m)Tc activity (x) (y=0.82x - 10(-5), R (2)=0.88). No toxicity was observed after nine weekly inhalations of a mean dose of gemcitabine of 11.1 mg (88% of the target dose) as assessed from scintigraphic data. A dose-dependent peak plasma concentration of gemcitabine (20-74 ng/ml) was observed by the tenth minute of inhalation. CONCLUSIONS: We have characterized a gemcitabine aerosol suitable for intrathoracic airway deposition and demonstrated that jet nebulization does not alter the cytotoxic properties of the drug. In a primate model, we have developed a scintigraphic procedure for the monitoring of aerosol deposition, and we have demonstrated the safety of nine weekly aerosol administrations of gemcitabine.

Aerosols↗

PubMed2005

In vitro study and semiempirical model for aerosol delivery control during mechanical ventilation.

The object of this study was to evaluate in vitro the influence of various ventilatory parameters on the delivery of synchronized nebulization of terbutaline during mechanical ventilation and to determine a semiempirical model to control the quantity of aerosol delivered into the patient's lung. An ATOMISOR NL9 M jet nebulizer (La Diffusion Technique Francaise, France) was filled with terbutaline (Bricanyl, Astra-Zeneca, Sweden) and connected to the inspiratory line of a Horus ventilator (Taema, France). Nebulization was synchronized with the inspiratory phase. We assessed at the end of the endotracheal tube the quantity of terbutaline (terbutaline mass output) and the volume median diameter (VMD) by diffraction-laser method. There was a negative correlation between terbutaline mass output and inspiratory air flow ( r =-0.95, p <0.0001) and between VMD and inspiratory air flow ( r =-0.96, p <0.0001). Moreover, positive end-expiratory pressure levels between 0 cm and 8 cm of water did not significantly change the terbutaline output mass ( p =0.22). Total nebulization time and terbutaline mass output calculated by the mathematical model showed good agreement with experimental data. In conclusion, our semiempirical model allows calculation of the duration of the nebulization required to deliver a given mass of terbutaline into patient lungs.

Aerosols↗

PubMed2005

Aerosol deposition in neonatal ventilation.

Lung deposition of inhaled drugs in ventilated neonates has been studied in models of questionable relevance. With conventional nebulizers, pulmonary deposition has been limited to 1% of the total dose. The objective of this study was to assess lung delivery of aerosols in a model of neonatal ventilation using a conventional and novel electronic micropump nebulizer. Aerosol deposition studies with 99mTc diethylenetriamine pentaacetate (99mTc-DTPA) were performed in four macaques (2.6 kg) that were ventilated through a 3.0-mm endotracheal tube (with neonatal settings (peak inspiratory pressure 12-14 mbar, positive end-expiratory pressure 2 mbar, I/E ratio 1/2, respiratory rate 40/min), comparing a jet-nebulizer MistyNeb (3-mL charge, 4.8 microm), an electronic micropump nebulizer operating continuously [Aeroneb Professional Nebulizer (APN-C); 0.5-mL charge, 4.6 microm], and another synchronized with inspiration [Aeroneb Professional Nebulizer Synchronized (APN-S); 0.5-mL charge, 2.8 microm]. The amount of radioactivity deposited into lungs and connections and remaining in the nebulizer was measured by a gamma counter. Despite similar amounts of 99mTc-DTPA in the respiratory circuit with all nebulizers, both APN-S and APN-C delivered more drug to the lungs than MistyNeb (14.0, 12.6, and 0.5% in terms of percentage of nebulizer charge, respectively; p = 0.006). Duration of delivery was shorter with APN-C than with the two other nebulizers (2 versus 6 and 10 min for the APN-S and the MistyNeb, respectively; p < 0.001). Electronic micropump nebulizers are more efficient to administer aerosols in an animal model of ventilated neonates. Availability of Aerogen's electronic micropump nebulizers offers new opportunities to study clinical efficacy and risks of aerosol therapy in ventilated neonates.

Administration, Inhalation↗

PubMed2005

Safety of pulmonary administration of gemcitabine in rats.

The purpose of this research was to evaluate the safety of pulmonary administration of gemcitabine and to determine the maximum tolerated dose by weekly pulmonary administrations in an animal model. Five groups of eight Wistar rats received gemcitabine at doses of 2, 4, 6, or 8 mg/kg or the vehicle solution by endotracheal spray with scintigraphic imaging of lung deposition. In order to document the safety of digestive exposure, five groups of eight rats received gemcitabine at the same dosages or the vehicle solution by gavage. Nine weekly sessions were planned, and blood cell counts and histological examinations were performed in live animals at day 64. Scintigraphic imaging confirmed pulmonary deposition in 310 of 316 spray administrations (98%) with homogeneous pattern of deposition. The maximum tolerated dose of gemcitabine by pulmonary administration was 4 mg/kg. At this dosage, administered once a week for 9 consecutive weeks, there were no chemotherapy-related deaths and no clinical, histological, or hematological signs of toxicity except for a decrease in platelet and red blood cell counts, with no clinical significance. The toxicity of gemcitabine was higher via oral than lung delivery in terms of weight loss and white blood cell toxicity at dosages of 2, 4, and 6 mg/kg. Pulmonary administration of gemcitabine is safe in rats at a maximum tolerated dose of 4 mg/kg once a week for 9 weeks. At an equivalent dosage, the toxicity of gemcitabine is lower by lung than oral administration.

Administration, Inhalation↗

PubMed2005

Effects of inhaled fenoterol and positive end-expiratory pressure on the respiratory mechanics of patients with chronic obstructive pulmonary disease.

BACKGROUND: During acute ventilatory failure in patients with chronic obstructive pulmonary disease (COPD), applying external positive end-expiratory pressure (PEEPe) will reopen small airways and, thus, may enhance peripheral deposition as well as the physiological effects of inhaled beta-2 agonists. OBJECTIVE: To investigate the efficacy of inhaled fenoterol applied by zero end-expiratory pressure (ZEEPe) or PEEPe. METHODS: Ten patients with COPD who were intubated and mechanically ventilated received fenoterol (10 mg/4 mL) via the ventilator using a jet nebulizer for 30 min on ZEEPe and PEEPe set at 80% of the total PEEP in a random order. The total resistance of the respiratory system (rapid airway occlusion technique), change in end-expiratory lung volume and expiratory flow limitation were assessed before and 5 min, 15 min, 30 min, 60 min and 240 min after fenoterol inhalation. RESULTS: Before inhalation and 60 min after inhalation, the total PEEP, the change in end-expiratory lung volume and the total resistance of the respiratory system were 8+/-3 cmH2O and 6+/-3 cmH2O, 0.61+/-0.34 L and 0.43+/-0.32 L, and 26+/-7 cmH2O/L/s and 23+/-6 cmH2O/L/s, respectively, with ZEEPe, and 9+/-3 cmH2O and 8+/-3 cmH2O (P<0.05 versus ZEEPe), 0.62+/-0.34 L and 0.62+/-0.37 L (P<0.05 versus ZEEPe), and 26+/-9 H2O/L/s and 25+/-9 H2O/L/s, respectively, with PEEPe. Three patients became not flow-limited under the combination of PEEPe and fenoterol. CONCLUSIONS: In patients with COPD, fenoterol combined with PEEPe has opposing effects on respiratory mechanics. First, it does not significantly reduce lung hyperinflation or inspiratory resistances. Second, it allows expiratory flow limitation reversal in some patients. These findings result from the net effect on end-expiratory lung volume of each intervention. This implies that if fenoterol is used in combination with PEEPe, the level of PEEPe should be reassessed during the time course of the drug to prevent any further lung hyperinflation.

Administration, Inhalation↗