Systemic availability and lung deposition of budesonide via three different nebulizers in adults

Dahlström, Kerstin; Thorsson, Lars; Larsson, Petter; Nikander, Kurt

doi:10.1016/s1081-1206(10)62146-1

Cited by 29 publications

(15 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Stomach radioactivity was not measured in the present study and, thus, any contribution from swallowed, absorbed radioactivity is unknown. However, the degree to which radioactivity in the oral cavity or gastrointestinal tract might have contributed to the systemic radioactivity absorbed from the lungs, was estimated, assuming a nebulizer delivery efficiency of 99m Tc‐DTPA as high as that of budesonide in a previous study [36]. In that study, a Pari nebulizer identical to the one in the present study and an aerosol administration technique aiming at maximal pulmonary delivery were used.…”

Section: Discussionmentioning

confidence: 99%

Site of deposition and absorption of an inhaled hydrophilic solute

Bondesson¹,

Bengtsson²,

Nilsson³

et al. 2007

Brit J Clinical Pharma

View full text Add to dashboard Cite

AimsTo characterize the absorption kinetics and bioavailability of an inhaled hydrophilic solute deposited at various sites within the airways. MethodsNine healthy nonsmokers received one intravenous, one oropharyngeal and two pulmonary doses of technetium-99 m-labelled diethylene triamine pentaacetic acid ( 99m Tc-DTPA) in an open and crossover fashion. Pulmonary doses were administered as nebulized large and fine droplet-sized aerosols by Pari and UltraVent nebulizers at fairly rapid and slow inhalation flows, respectively. Plasma concentration-time profiles and 24 h urinary excretion of radioactivity were determined. One dose of 99m Tc-labelled Nanocoll, as a marker of mucociliary clearance (MCC), was also administered by Pari for similar lung deposition as the 99m Tc-DTPA and followed by repeated chest g-imaging. Results Intrapulmonary deposition patterns of99m Tc-DTPA differed significantly (the mean ratio of penetration index (Pari : UltraVent) was 76% with 95% CI 63%, 91%). However, no differences in rate or extent of 99m Tc-DTPA absorption were detected. Mean absorption time was 1.8 h (mean difference (Pari-UltraVent): -0.1 h with 95% CI -0.6 h, 0.3 h) and the bioavailability was 70% (mean ratio (Pari : UltraVent): 101% with 95% CI 90%, 115%). The pulmonary elimination half-life of 99m Tc-Nanocoll (8 h and 45 min) was significantly longer than that of 99m Tc-DTPA (less than 2 h). The oral bioavailability of 99m Tc-DTPA was estimated to be 3.1%. ConclusionsThe main elimination pathway of the inhaled hydrophilic solute 99m Tc-DTPA from the lungs is trans-epithelial absorption. Despite different intrapulmonary radioaerosol deposition patterns, as verified by gamma scintigraphy, no differences in 99m Tc-DTPA absorption kinetics or bioavailability were detected.

show abstract

Section: Discussionmentioning

confidence: 99%

Site of deposition and absorption of an inhaled hydrophilic solute

Bondesson¹,

Bengtsson²,

Nilsson³

et al. 2007

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…With those fractions included in a calculation of the lung deposition in percent of the emitted dose, the lung deposition would have ranged from 50 to 51%. This means that there was a considerable difference in lung deposition between the I-neb AAD System in TBM, and the conventional jet nebulizers in the Dahlstrom et al (15) study, although the latter were used optimally, that is, either breath-actuated or with a rebreathing bag. The large differences in lung deposition could be attributed to the pulsed aerosol delivery in TBM with the pause for aerosol deposition before each exhalation, and possibly also to the differences in techniques used, that is, g-scintigraphy versus pharmacokinetics.…”

Section: I-neb Tbm Versus Tim Breathing Pattern and Lung Deposition S-41mentioning

confidence: 98%

“…Lung deposition of nebulized 99m Tc-DPTA has in previous studies with nebulizers been expressed in percent of the nominal dose (nebulizer fill), which makes a comparison with the present results expressed as percent of emitted dose difficult. The exception is the study by Dahlstrom et al, (15) in which lung deposition of nebulized budesonide during tidal breathing was determined by a pharmacokinetic method, and expressed both in percent of nominal dose and as ''doseto-subject.'' The mean lung deposition of budesonide expressed in percent of nominal dose ranged from 14-16%, and in percent of dose-to-subject from 36-59%.…”

Section: I-neb Tbm Versus Tim Breathing Pattern and Lung Deposition S-41mentioning

confidence: 99%

Mode of Breathing—Tidal or Slow and Deep—through the I-neb Adaptive Aerosol Delivery (AAD) System Affects Lung Deposition of^99mTc-DTPA

Nikander

Prince

Coughlin

et al. 2010

Journal of Aerosol Medicine and Pulmonary Drug Delivery

Self Cite

View full text Add to dashboard Cite

Background: The I-neb AAD System was designed to deliver aerosol with two different breathing pattern algorithms: the Tidal Breathing Mode (TBM) and the Target Inhalation Mode (TIM). For the purpose of the study, the TBM breathing pattern algorithm was set to guide the subjects to inhalation during tidal breathing with aerosol pulsed during 50-80% of the time spent on inhalation, whereas the TIM breathing pattern was set to guide the subject to a slow and deep inhalation of up to *9 sec with aerosol pulsed for up to 7 sec, leaving 2 sec for particle deposition in the lungs. In TIM, the inspiratory flow was guided to *20 L=min through a built-in resistance in the mouthpiece. Methods: We have, in a randomized, open-label, crossover study of 12 healthy subjects evaluated lung deposition following administration of a radiolabeled aerosol from the I-neb AAD System with the TBM and TIM breathing patterns. Results:The results showed that mean lung deposition was significantly higher when using the I-neb AAD System with the TIM breathing pattern (73.3%) than with the TBM breathing pattern (62.8%). The mean exhaled fractions were low (<1%) for both breathing patterns. The nebulization time was significantly shorter with the TIM breathing pattern (3.0 min) than with the TBM breathing pattern (4.7 min). Conclusions:The results of the present study showed that lung deposition with the slow and deep inhalation achieved through the I-neb AAD System in TIM was superior to the lung deposition achieved during tidal breathing in TBM. With the combination of high lung deposition, almost no loss of aerosol during exhalation, and short nebulization time the I-neb AAD System with the TIM breathing pattern should be of special value to patients who require multiple daily dosing of aerosolized medication, are using drugs that should not be wasted into the room air, or would benefit from a more efficient delivery system.

show abstract

“…Budesonide suffer extensive first-pass metabolism in the liver originating metabolites of minimal activity. The systemic bioavailability of budesonide is considered low after oral (6-13%) and topical (15-17%) administration and its half-life in human plasma after nasal inhalation is 2.9 ± 0.4 h [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Budesonide quantification by HPLC coupled to atmospheric pressure photoionization (APPI) tandem mass spectrometry. Application to a comparative systemic bioavailability of two budesonide formulations in healthy volunteers

Borges

Astigarraga

Sverdloff

et al. 2011

Journal of Chromatography B

View full text Add to dashboard Cite

Systemic availability and lung deposition of budesonide via three different nebulizers in adults

Cited by 29 publications

References 20 publications

Site of deposition and absorption of an inhaled hydrophilic solute

Site of deposition and absorption of an inhaled hydrophilic solute

Mode of Breathing—Tidal or Slow and Deep—through the I-neb Adaptive Aerosol Delivery (AAD) System Affects Lung Deposition of^99mTc-DTPA

Budesonide quantification by HPLC coupled to atmospheric pressure photoionization (APPI) tandem mass spectrometry. Application to a comparative systemic bioavailability of two budesonide formulations in healthy volunteers

Contact Info

Product

Resources

About

Systemic availability and lung deposition of budesonide via three different nebulizers in adults

Cited by 29 publications

References 20 publications

Site of deposition and absorption of an inhaled hydrophilic solute

Site of deposition and absorption of an inhaled hydrophilic solute

Mode of Breathing—Tidal or Slow and Deep—through the I-neb Adaptive Aerosol Delivery (AAD) System Affects Lung Deposition of99mTc-DTPA

Budesonide quantification by HPLC coupled to atmospheric pressure photoionization (APPI) tandem mass spectrometry. Application to a comparative systemic bioavailability of two budesonide formulations in healthy volunteers

Contact Info

Product

Resources

About

Mode of Breathing—Tidal or Slow and Deep—through the I-neb Adaptive Aerosol Delivery (AAD) System Affects Lung Deposition of^99mTc-DTPA