Urinary excretion reflects lung deposition of aminoglycoside aerosols in cystic fibrosis

Dequin, Pierre‐François; Faurisson, François; Lemarié, É.; Delatour, F; Marchand, Sophie; Valat, C; Boissinot, E; Gialluly, C. de; Diot, Patrice

doi:10.1183/09031936.01.99086801

Cited by 34 publications

(14 citation statements)

References 20 publications

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“…24 The fact that urinary excretion actually reflects the lung deposition was confirmed earlier for the aminoglycoside, amikacin which, like SCG, is absorbed from the lungs but not orally. Typically, following inhalation of a radiolabeled aerosol, Dequin et al 25 found that a close correlation existed between the mass of drug deposited in the lungs (MDL) as determined by means of scintigraphy and the cumulative amount of amikacin excreted in urine.…”

Section: Discussionmentioning

confidence: 98%

Lung Deposition in Cystic Fibrosis Patients Using an Ultrasonic or a Jet Nebulizer

Köhler

Sollich²,

Schuster-Wonka³

et al. 2003

Journal of Aerosol Medicine

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This study was conducted to compare pulmonary deposition following inhalation with an ultrasonic and a jet nebulizer in CF patients under conditions relevant to practice. The marker substance used to estimate the relative lung bioavailability was sodium cromoglycate (SCG), which is poorly absorbed from the gastrointestinal tract, but is completely absorbed from the lungs. Ten CF patients (aged 9-21 years) used an ultrasonic nebulizer (Multisonic compact 2.4 MHz) and a jet nebulizer (Parimaster, LC Plus Turbo) in a crossover design to inhale a solution containing 20 mg of SCG and a beta(2)-agonist. Urine was collected in five fractions until 12 h p. a., and the excreted SCG was determined by means of HPLC. Prior to each inhalation, the patients' pulmonary function was measured employing a Pneumoscope. Using the ultrasonic nebulizer, the amount of SCG excreted in urine was significantly greater than that after inhalation with the jet nebulizer (1.43 +/- 0.47 mg vs. 1.04 +/- 0.47 mg; p = 0.002), despite the larger residual volume in the ultrasonic nebulizer. The absorption half-life for SCG following ultrasonic nebulization was significantly shorter when compared with jet nebulization (84 +/- 14 min vs. 101 +/- 19 min; p = 0.005), being suggestive of a more peripheral deposition. Furthermore, an inverse relationship was found between absorption half-life and FEV(1) (% pred.) (r = -0.655, p = 0.04) or MMEF(75/25) (% pred.) (r = -0.844, p = 0.031), but only with the ultrasonic nebulizer. In conclusion, the ultrasonic nebulizer tested when used for inhalation in CF patients was found to be at least equivalent to the jet nebulizer.

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Section: Discussionmentioning

confidence: 98%

Lung Deposition in Cystic Fibrosis Patients Using an Ultrasonic or a Jet Nebulizer

Köhler

Sollich²,

Schuster-Wonka³

et al. 2003

Journal of Aerosol Medicine

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“…Given the known safety profile of atropine (Volans, 1996), a critical patient may be nebulized twice in the first hour to produce sufficient atropinization, enough for him to be carried to the hospital for conventional treatment, which is the intravenous bolus route. Since systemic pharmacokinetics of any inhaled drug reflects its deposition in distal pulmonary regions (Dequin et al, 2001;Kumar et al, 2011), systemic absorption of nebulized AS proves that its absorption is also occurring mainly at the alveolar level, giving an additional proof of antidote's deep penetration into the lung parenchyma, and emphasizing its role in neutralizing inhaled toxicant in the lungs itself.…”

Section: Discussionmentioning

confidence: 99%

Development and clinical study of submicronic-atropine sulphate respiratory fluid as a novel organophosphorous poisoning antidote

et al. 2014

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Context: Increased use of organophosphate insecticides (OPI) and possibility of terror groups using stocks of nerve agents underscore the need to develop effective and safe antidotes. While intramuscular administration of antidotes like atropine sulphate (AS) has certain lacunae, intravenous route may not be always feasible in emergency field conditions. Objective: Objective was (a) to develop a novel inhalable submicronic-AS respiratory fluid as potential antidote for OPI poisoning, (b) in-vitro and in-vivo evaluation in terms of respiratory fraction, and (c) clinical study to assess drug bioavailability in blood and atropinization pattern post-inhalation. Methods: Formulation was optimized on the basis of particle size of aerosolized droplets and in-vitro nebulization rate. Anderson cascade impaction (ACI) studies were carried out to validate the advantage of test formulation in terms of respirable fraction. Six healthy volunteers were inhaled the test formulation and blood bioavailability and atropinization were noted serially. Gamma scintigraphy was used to quantify total and regional lung deposition of nebulized AS in-vivo. Results: The formulation was optimized using 30% ethanol-saline with particle size in the range of 350-500 nm. In-vitro ACI data showed high respirable fraction (82.6 ± 3.1%) for the test formulation. In-vivo scintigraphy suggested whole lung deposition of 80.2 ± 6.8% of the total inhaled dose. Early blood bioavailability and atropinization pattern confirmed that therapeutic concentration of the drug in blood was reached within 5 min. Conclusions: 3% submicronic-AS respiratory fluid might be used as potential prophylactic/ therapeutic option against OPI poisoning with several advantages over intramuscular injection, including early blood bioavailability and atropinization.

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“…For example, an intrathoracic deposition of~85% of the emitted aerosol (particle mass) was measured of which~77% was deposited in the peripheral lung [146]. A lung dose can be estimated by measuring the cumulative excretion of the drug during 24 h in the urine [147][148][149][150] or by radiodeposition studies [139,141,142,[151][152][153][154][155][156][157][158][159]. For newly developed inhalers, theoretical equivalent doses to current, standard inhalation treatment have been calculated, based on in vitro testing [160,161] or using a dose escalating method [162].…”

Section: Lung Dosementioning

confidence: 99%

Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis: A European consensus

Heijerman

Westerman

Conway

et al. 2009

Journal of Cystic Fibrosis

228

180

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In cystic fibrosis inhalation of drugs for the treatment of CF related lung disease has been proven to be highly effective. Consequently, an increasing number of drugs and devices have been developed for CF lung disease or are currently under development. In this European consensus document we review the current status of inhaled medication in CF, including the mechanisms of action of the various drugs, their modes of administration and indications, their effects on lung function, exacerbation rates, survival and quality of life, as well as side effects. Specifically we address antibiotics, mucolytics/mucous mobilizers, anti-inflammatory drugs, bronchodilators and combinations of solutions. Additionally, we review the current knowledge on devices for inhalation therapy with regard to optimal particle sizes and characteristics of wet nebulisers, dry powder and metered dose inhalers. Finally, we address the subject of testing new devices before market introduction.

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Urinary excretion reflects lung deposition of aminoglycoside aerosols in cystic fibrosis

Cited by 34 publications

References 20 publications

Lung Deposition in Cystic Fibrosis Patients Using an Ultrasonic or a Jet Nebulizer

Lung Deposition in Cystic Fibrosis Patients Using an Ultrasonic or a Jet Nebulizer

Development and clinical study of submicronic-atropine sulphate respiratory fluid as a novel organophosphorous poisoning antidote

Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis: A European consensus

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