ABSTRACT
Drug delivery from a Dry Powder Inhaler (DPI) is dependent on the peak inspiratory flow rate (PIFR) generated. Currently available methods for estimating PIFR from most DPIs are limited and mainly rely on subjective assessment. We aim to show that spirometric and Diskus™ PIFR and Inspiratory Vital Capacity (IVC) are related to the underlying respiratory condition and that spirometric PIFR can be used to assess whether Diskus™ PIFR will be adequate when using this DPI. Healthy volunteers and patients with asthma, COPD, neuromuscular disease and non-respiratory disorders were recruited (n = 85). Demographics and baseline lung function by spirometry were recorded. Flow and volume readings were taken while patients used a Diskus™ DPI, housed in an airtight container connected to a spirometer. T-tests were performed to compare mean spirometric and Diskus™ PIFR/ IVC between groups. Stepwise regression analysis of Diskus™ PIFR versus spirometric PIFR, spirometric IVC, age, gender, condition, BMI, FEV1 and FVC was performed. The Diskus™ PIFR for the COPD and Neuromuscular Disease group was more than 10 L/min lower than the Healthy or Asthma groups (p < 0.05). The mean spirometric and Diskus™ IVC of the Healthy group was significantly (>0.75 L) higher than the mean for the other three groups (p < 0.05). Diskus™ PIFR was moderately correlated with spirometric PIFR and age (Adjusted R(2) = 0.58, p < 0.0001). PIFR generated using a Diskus™ DPI is dependent on the underlying disease and age. A spirometric PIFR of less than 196 L/min should prompt further investigation into the suitability of a patient for a Diskus™ DPI, with possible consideration of alternate devices.
ABSTRACT
PURPOSE: Some patients are unable to generate the peak inspiratory flow rate (PIFR) necessary to de-agglomerate drug particles from dry powder inhalers (DPIs). In this study we tested the hypothesis that the acoustic parameters of an inhalation are related to the PIFR and hence reflect drug delivery. METHODS: A sensitivity analysis of the relationship of the acoustics of inhalation to simultaneously recorded airflow, in a cohort of volunteers (n = 92) was performed. The Next Generation Impactor (NGI) was used to assess in vitro drug delivery from salmeterol/fluticasone and salbutamol Diskus™ DPIs. Fine particle fraction, FPF, (<5 µm) was measured at 30-90 l/min for 2-6 s and correlated with acoustically determined flow rate (IFRc). In pharmacokinetic studies using a salbutamol (200 µg) Diskus™, volunteers inhaled either at maximal or minimal effort on separate days. RESULTS: PIFRc was correlated with spirometrically determined values (R (2) = 0.88). In in vitro studies, FPF increased as both flow rate and inhalation duration increased for the salmeterol/fluticasone Diskus™ (Adjusted R (2) = 0.95) and was proportional to flow rate only for the salbutamol Diskus™ (Adjusted R (2) = 0.71). In pharmacokinetic studies, blood salbutamol levels measured at 20 min were significantly lower when PIFRc was less than 60 l/min, p < 0.0001. CONCLUSION: Acoustically-determined PIFR is a suitable method for estimating drug delivery and for monitoring inhalation technique over time.
