In vitro and in vivo aspects of quantifying intrapulmonary deposition of a dry powder radioaerosol

Bondesson, Eva; Asking, Lars; Borgström, Lars; Nilsson, Lars‐Erik; Trofast, Eva; Wollmer, Per

doi:10.1016/s0378-5173(01)00898-5

Cited by 13 publications

(3 citation statements)

References 21 publications

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“…The intrapulmonary aerosol deposition pattern of radioactivity within the right lung was established as a penetration index (PI) defined as the ratio of peripheral to central lung zone deposition, calculated on the basis of a previously described method [26]. Total pulmonary deposition (Dose lung ) was calculated as radioactivity in the right lung multiplied by 1.9, as described previously [27].…”

Section: Methodsmentioning

confidence: 99%

Site of deposition and absorption of an inhaled hydrophilic solute

Bondesson¹,

Bengtsson²,

Nilsson³

et al. 2007

Brit J Clinical Pharma

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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.

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Section: Methodsmentioning

confidence: 99%

Site of deposition and absorption of an inhaled hydrophilic solute

Bondesson¹,

Bengtsson²,

Nilsson³

et al. 2007

Brit J Clinical Pharma

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“…Total pulmonary deposition was calculated as the percentage of radioactivity in the right lung multiplied by 1.9, for reasons previously discussed (19).…”

Section: Assessments ( 99m Tc-dtpa Administrations Only)mentioning

confidence: 99%

Effects of Sodium Taurocholate on the Absorption of Inhaled 99mTc-DTPA

et al. 2006

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“…In previous studies of inhaled dry powders, aerosol distribution within the lungs as estimated using planar gamma scintigraphy was found either to be quite insensitive to changes in aerosol particle size or inhalation flow, or to depend on the total pulmonary aerosol deposition. [2][3][4][5] Unless a more sophisticated imaging method such as single photon emission computed tomography (SPECT) could be applied to discriminate better between peripheral and central pulmonary deposition patterns, other factors, or a combination thereof, to a greater extent influencing the regional distribution of aerosol within the lung would have to be sought.…”

Section: Introductionmentioning

confidence: 99%

Dose Delivery Late in the Breath Can Increase Dry Powder Aerosol Penetration into the Lungs

Bondesson

Bengtsson

Borgström

et al. 2005

Journal of Aerosol Medicine

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In addition to aerosol particle size and mode of inhalation, the time-point of dose delivery during inhalation may be an important factor governing the intrapulmonary distribution of aerosolized drug. To generate different intrapulmonary deposition patterns of a drug model aerosol, a device with the capability of delivering small amounts of technetium-99m-labeled lactose dry powder at pre-set time-points during inhalation was developed. A single dose of the radioaerosol was delivered after inhalation of 20% (A) or 70% (B) of the vital capacity inhaled through the device. Twelve healthy subjects were studied in a randomized crossover fashion. Planar gamma scintigraphy was carried out, and the penetration index, PI, defined as the ratio of peripheral to central lung zone deposition of radioactivity, was estimated. A significant increase in PI from 3.0 (A) to 3.7 (B) was observed with the change from early to late delivery of the dose (p < 0.01). No difference in the total amount of radioactivity within the lungs could be detected. In conclusion, independent of total pulmonary deposition, deeper dry powder aerosol penetration into the lungs was found for the dose delivered at near end instead of at the beginning of inhalation. By computational modeling of the aerosol transport and deposition, that finding was mechanistically explained by differences in airway caliber as a consequence of the level of lung inflation at the time-point of dose delivery.

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In vitro and in vivo aspects of quantifying intrapulmonary deposition of a dry powder radioaerosol

Cited by 13 publications

References 21 publications

Site of deposition and absorption of an inhaled hydrophilic solute

Site of deposition and absorption of an inhaled hydrophilic solute

Effects of Sodium Taurocholate on the Absorption of Inhaled 99mTc-DTPA

Dose Delivery Late in the Breath Can Increase Dry Powder Aerosol Penetration into the Lungs

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