Lung deposition of budesonide inhaled via Turbuhaler: a comparison with terbutaline sulphate in normal subjects

Abstract

We wanted to evaluate whether lung deposition of budesonide and terbutaline sulphate differs, and to determine lung deposition of budesonide inhaled at different peak inspiratory flows, through Turbuhaler. Lung deposition of budesonide, a lipophilic substance, and of terbutaline sulphate, a hydrophilic substance, was therefore compared, after administration via an inspiratory flow-driven, multi-dose, powder inhaler (Turbuhaler, Astra Draco AB) to 10 healthy volunteers. The radionuclide 99mTc was used to label drug particles, and radioactivity, indicating drug deposition, was measured using a gamma camera. Budesonide was inhaled at a normal flow of 58 l.min-1 and at a slow flow of 36 l-min-1. At the faster flow, a mean +/- SD 27.7 +/- 9.5% of the metered dose was deposited in the lung and at the slower flow 14.8 +/- 3.3% was deposited (p < 0.001). Mean lung deposition of terbutaline sulphate inhaled at 57 l.min-1 was 27.0 +/- 7.7%. We conclude that inspiratory flow has an important effect on lung deposition, but water solubility appears to have no effect.

Pharmacokinetics and systemic activity of fluticasone via Diskus® and pMDI, and of budesonide via Turbuhaler®

“…In earlier studies, the total lung deposition of budesonide via Turbuhaler was found to be comparable in healthy subjects (28%) [28] and patients (26%) with mild to moderate asthma (forced expiratory volume in 1 second, 50±92% of predicted) [29], and appears to be more or less unaffected by the disease. A more central deposition was, however, found in the asthmatic patients, with a peripheral vs central ratio of 0.64, compared with 1.72 in healthy subjects, which suggests that peripheral aerosol penetration of budesonide via Turbuhaler is lower in asthmatic patients.…”

Inhaler technique and training in people with chronic obstructive pulmonary disease and asthma

“…Borgstrom et al demonstrated that the percentage of the metered dose from a budesonide Turbohaler deposited in the lung as measured by gamma scintigraphy increased from a mean ± standard deviation 14.8 ± 3.3% at an inspiratory flow rate of 36 l/min to 27.7 ± 9.5% at 58 l/min [50]. A further study highlighted the variability in dose delivered by the Turbohaler device, by demonstrating that the fine particle fraction was more strongly influenced by inspiratory flow rate through a Turbohaler compared with an Accuhaler (12-24% at 30-60 l/min vs 15-21% at 30-90 l/min, respectively) [51].…”

“…Faster inspiratory flow rates increase inertial impaction of aerosols in the oropharynx and at bifurcations in the large central airways, thus reducing lung deposition in the peripheral airways. In one study determining whole lung deposition using the charcoal block method, deposition of radiolabeled terbutaline was reduced by a third by increasing the airflow through the MDI device from 30 to 180 l/min (mean ± standard deviation: 11.2 ± 4.0 vs 7.2 ± 2.2; p < 0.05) [50]. A significant proportion of patients with asthma and COPD have been shown to have an inspiratory flow too high for an MDI, which could potentially reduce the clinical effectiveness of inhaled drugs [20,21].…”

“…Patients who use any particular inhaler device, but cannot achieve the optimum inspiratory flow rate, will often gain clinical benefit from that device (assuming that their overall technique is satisfactory), but potentially not the maximum benefit. For example, if a patient can only inhale through a Turbohaler device at an inspiratory flow rate of 36 l/min, approximately 15% of the metered dose will reach the lungs, but if the inspiratory flow rate can be increased to 56 l/min then lung deposition will almost double to approximately 28% [50]. It is likely that patients will achieve a clinical benefit at both inspiratory flow rates, but would seem inherently obvious that they could potentially gain greater benefit at the higher flow rate owing to greater lung deposition.…”

Ciclesonide is more effective than budesonide in the treatment of persistent asthma

“…[23] In contrast, pulmonary deposition of budesonide via dry powder inhaler is lower (15%-28% of the administered dose) and deposition is localised primarily to the central region of the lung. [25,26] Furthermore, the active metabolite of ciclesonide (des-CIC) has a high relative glucocorticoid receptor affinity (1200 versus 900 for budesonide; dexamethasone reference is 100) and possesses substantial anti-inflammatory activity. [24,27] …”