In Vitro Determination of Respimat® Dose Delivery in Children: An Evaluation Based on Inhalation Flow Profiles and Mouth–Throat Models
Open Access
- 1 February 2016
- journal article
- research article
- Published by Mary Ann Liebert Inc in Journal of Aerosol Medicine and Pulmonary Drug Delivery
- Vol. 29 (1), 76-85
- https://doi.org/10.1089/jamp.2014.1166
Abstract
Background: Aerosol therapy in young children can be difficult. A realistic model based on handling studies and in vitro investigations can complement clinical deposition studies and be used to enable dose-to-the-lung (DTL) predictions. Methods: Predictions on dose delivery to the lung were based on (1) representative inhalation flow profiles from children enrolled in a Respimat® handling study, (2) in vitro measurement of the fine-particle DTL using mouth–throat models derived from nuclear magnetic resonance/computed tomography (NMR/CT) scans of children, and (3) a mathematical model to predict the tiotropium DTL. Accuracy of the prediction was confirmed using pharmacokinetic (PK) data from children with cystic fibrosis enrolled in a phase 3 clinical trial of tiotropium Respimat with valved holding chamber (VHC). Results: Representative inhalation flow profiles for each age group were obtained from 56 children who successfully inhaled a volume >0.15 L from the Respimat with VHC. Average dimensions of the mouth–throat region for 38 children aged 1–in vitro measurement and were 5.1±1.1%, 15.6%±1.4%, 17.9%±1.5%, and 37.1%±1.8% of the delivered dose for child models 0–in vitro DTL per body mass (μg/kg [±SD]) were 0.031±0.014, 0.066±0.031, 0.058±0.024, and 0.059±0.029, respectively, compared to 0.046 in adults. Therefore, efficacy of the treatment was not negatively impacted in spite of the seemingly low percentages of the DTL. Conclusions: We conclude that the combination of real-life inhalation profiles with respective mouth–throat models and in vitro determination of delivered DTL is a good predictor of the drug delivery to children via the Respimat with VHC. The data provided can be used to support data from appropriate clinical trials.Keywords
This publication has 20 references indexed in Scilit:
- Impact of patients' satisfaction with their inhalers on treatment compliance and health status in COPDRespiratory Medicine, 2013
- What the pulmonary specialist should know about the new inhalation therapiesEuropean Respiratory Journal, 2011
- Importance of inhaler-device satisfaction in asthma treatment: Real-world observations of physician-observed compliance and clinical/patient-reported outcomesAdvances in Therapy, 2011
- Patient preferences for inhaler devices in chronic obstructive pulmonary disease: experience with Respimat® Soft Mist™ InhalerInternational Journal of Chronic Obstructive Pulmonary Disease, 2009
- Ethical issues of clinical trials in children: a European perspectiveArchives of Disease in Childhood, 2009
- Importance of inhaler devices in the management of airway diseaseRespiratory Medicine, 2008
- The future for lung disease in childrenThorax, 2007
- Comparison of the Aerosol Velocity and Spray Duration of Respimat® Soft Mist™ Inhaler and Pressurized Metered Dose InhalersJournal of Aerosol Medicine, 2005
- Satisfaction with Medication: An Overview of Conceptual, Methodologic, and Regulatory IssuesValue in Health, 2004
- Validation of a general measure of treatment satisfaction, the Treatment Satisfaction Questionnaire for Medication (TSQM), using a national panel study of chronic diseaseHealth and Quality of Life Outcomes, 2004