Chest
Volume 122, Issue 2, August 2002, Pages 510-516
Journal home page for Chest

Clinical Investigations
ASTHMA
Lung Deposition of Hydrofluoroalkane-134a Beclomethasone Is Greater Than That of Chlorofluorocarbon Fluticasone and Chlorofluorocarbon Beclomethasone: A Cross-over Study in Healthy Volunteers

https://doi.org/10.1378/chest.122.2.510Get rights and content

Study objectives

To compare the lung deposition of radiolabeled hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP) with chlorofluorocarbon fluticasone propionate (CFC-FP) and chlorofluorocarbon beclomethasone (CFC-BDP).

Design

Six-day, open-label, nonrandomized, crossover study.

Setting

Clinical research laboratory.

Participants

Nine healthy, nonsmoking, adult volunteers.

Interventions

On each study day, participants inhaled one or two puffs of 99mTc-labeled HFA-BDP, CFC-FP, or CFC-BDP. All products delivered 50 μg per puff ex-valve. Subjects used a respiratory training and monitoring device to meet predefined, standardized inhalation patterns. Immediately after inhalation of radiolabeled study drug, planar gamma camera images were obtained.

Measurements and results

Radiolabeled HFA-BDP had a higher deposition in the lungs (53% ex-actuator) compared with CFC-FP (12 to 13%) and CFC-BDP (4%). Conversely, CFC-FP and CFC-BDP had a much higher distribution to the oropharynx (72 to 78%, and 82%, respectively) than HFA-BDP (29%). HFA-BDP was deposited evenly throughout the lungs, while CFC-FP and CFC-BDP deposition was primarily in the large central and intermediate airways. Andersen particle size sampling gave mass median aerodynamic diameters for HFA-BDP, CFC-FP, and CFC-BDP of 0.9 μm, 2.0 μm, and 3.5 μm, respectively.

Conclusions

Lung deposition was greater with HFA-BDP compared with CFC-FP and CFC-BDP. Deposition values appeared to be related to the particle size distribution of each inhaler, with the smaller particles of HFA-BDP providing the greatest lung deposition and least oropharyngeal deposition.

Section snippets

Subject Selection and Training

Men and women from 18 to 55 years of age, between 155 cm and 190 cm in height, and within 25% of normal body weight for their height and frame size were eligible for inclusion in the study. Subjects were required to have abstained from tobacco for at least 1 year and have a < 10-pack-year smoking history. Subjects were also required to have an FEV1 at the screening visit ≥ 90% of predicted normal. In addition, women were required to have a negative urine pregnancy test result and be using a

Study Subjects

Out of 16 subjects screened, 9 subjects (5 men and 4 women) enrolled in and completed the study. Mean FEV1 was 3.8 L (SD, 0.7 L; range, 2.7 to 4.8 L). Mean FEV1 percent predicted was 98.4% (SD, 8.4%; range, 90.2 to 113.3%). Data from the respiratory feedback device demonstrated that mean breath patterns were consistent between study days and that subjects achieved the target breath patterns (Table 1).

Radiolabeling Validation

Figure 1shows the radiolabeling validation results for HFA-BDP, CFC-BDP, and CFC-FP. The

Discussion

In this study, a larger proportion of inhaled HFA-BDP reached the lungs compared with CFC-FP and CFC-BDP. With HFA-BDP, 53% of the ex-actuator dose was deposited in the lungs compared with 12 to 13% for CFC-FP and only 4% for CFC-BDP. Additionally, less HFA-BDP impacted and remained in the oropharynx and was subsequently swallowed compared with CFC-FP and CFC-BDP. Furthermore, HFA-BDP appeared to be deposited evenly throughout the lungs, including the large, intermediate, and small airways,

References (28)

Cited by (211)

  • Metered dose inhalers (MDIs)

    2021, Inhaled Medicines: Optimizing Development through Integration of In Silico, In Vitro and In Vivo Approaches
  • Development of human respiratory airway models: A review

    2020, European Journal of Pharmaceutical Sciences
View all citing articles on Scopus

This study was sponsored by 3M Pharmaceuticals, St. Paul, MN.

Dr. Leach was an employee of 3M Pharmaceuticals from 1990 to 2000, during which time the study was conducted. He is no longer employed by 3M. Dr. Leach owned stock in 3M during that period of time and continues to hold a portion of that stock. Since 1993, Ms. Davidson has been an employee of 3M Pharmaceuticals and has owned stock in 3M. Dr. Hasselquist has been an employee of the University of Minnesota since October 1990 and was a paid consultant to 3M during the time the study was conducted. Dr. Hasselquist does not own any stock in 3M or have any other financial interest in the company. Dr. Boudreau was a paid consultant at 3M Pharmaceuticals during the time the study was conducted. Dr. Boudreau does not own any negotiable securities (eg, stocks) in 3M Corporation or its subsidiaries.

View full text