WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Use of a spacer minimizes oropharyngeal deposition and optimizes drug targeting to the airways in subjects with coordination difficulties. However, the increase in pulmonary deposition often observed with spacer devices, could potentially lead to an increase in overall systemic exposure.• EMA guidelines recommend that the development of a pMDI should always include testing of at least one specific spacer for use with a particular pMDI.• The aim of this study was to examine the effect of AeroChamber Plus™ on the lung bioavailability and total systemic exposure of a hydrofluoroalkane (HFA) pMDI fixed combination of extra‐fine beclometasone dipropionate/formoterol (100/6 µg) (Foster®).WHAT THIS STUDY ADDS• The use of AeroChamber Plus™ optimizes the lung delivery of beclometasone and formoterol in subjects that find it difficult to synchronize aerosol actuation with the inspiration of breath.• The total systemic exposure of beclometasone 17‐monopropionate and formoterol was not significantly increased by the use of the AeroChamber Plus™ spacer.• Use of the AeroChamber Plus™ spacer device with the extra‐fine beclometasone dipropionate/formoterol (100/6 µg) fixed combination pMDI can be a valuable option for certain patients groups, such as subjects with difficulties in achieving an adequate inhalation technique.AIM To assess the effect of AeroChamber Plus™ on lung deposition and systemic exposure to extra‐fine beclometasone dipropionate (BDP)/formoterol (100/6 µg) pMDI (Foster®). The lung deposition of the components of the combination given with the pMDI was also evaluated using the charcoal block technique.METHODS Twelve healthy male volunteers received four inhalations of extra‐fine BDP/formoterol (100/6 µg) using (i) pMDI alone, (ii) pMDI and AeroChamber Plus™ and (iii) pMDI and charcoal ingestion.RESULTS Compared with pMDI alone, use of AeroChamber Plus™ increased the peak plasma concentrations (Cmax) of BDP (2822.3 ± 1449.9 vs. 5454.9 ± 3197.1 pg ml−1), its active metabolite beclometasone 17‐monopropionate (17‐BMP) (771.6 ± 288.7 vs. 1138.9 ± 495.6 pg ml−1) and formoterol (38.4 ± 17.8 vs. 54.7 ± 20.0 pg ml−1). For 17‐BMP and formoterol, the AUC(0,30 min), indicative of lung deposition, was increased in the AeroChamber Plus™ group by 41% and 45%, respectively. This increase was mainly observed in subjects with inadequate inhalation technique. However, use of AeroChamber Plus™ did not increase the total systemic exposure to 17‐BMP and formoterol. Results after ingestion of charcoal confirmed that AUC(0,30 min) can be taken as an index of lung bioavailability and that more than 30% of the inhaled dose of extra‐fine BDP/formoterol 100/6 µg was delivered to the lung using the pMDI alone.CONCLUSIONS The use of AeroChamber Plus™ optimizes the delivery of BDP and formoterol to the lung in subjects with inadequate inhalation technique. The total systemic exposure was not increased, supporting the safety of extra‐fine BDP/formoterol pMDI with AeroChamber Plus™.
PurposeLeber Hereditary Optic Neuropathy (LHON) is a mitochondrial genetic disorder causing severe, bilateral loss of visual acuity (VA). Idebenone is the only treatment for LHON currently approved in Europe. Due to the rarity of the disease, information about outcome in patients starting treatment >12 months since disease onset in the most recent eye (chronic LHON) is scarce.MethodsThe search for clinical evidence included any published study or conference abstract evaluating oral idebenone at the approved dose of 900 mg/day, in patients with confirmed diagnosis of LHON starting treatment >12 months since disease onset in the most recent eye. Literature search was carried out on Medline, Embase, InsightMeme and Cochrane Libraries up to March 2020.ResultsEvidence for idebenone treatment of chronic LHON is based on four uncontrolled, retrospective case series and one post‐hoc analysis of a randomized controlled study. All studies included patients (n = 4–53) with confirmed primary LHON mutations and evaluated changes in VA with the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The post‐hoc analysis (n = 53, idebenone:34; placebo:19) assessed efficacy as rate of clinically relevant recovery (CRR; defined as improvement from off‐chart to reading five letters, or improvement of 10 letters) from baseline (BL) after 6‐month therapy. 35.3% of idebenone‐treated versus 10.5% of placebo patients achieved CRR (p = 0.059); by eyes: 23.5% versus 5.3% (p = 0.016). All 4 retrospective studies (n = 4–16) assessed efficacy as average VA improvement (all eyes) from BL after 9 to 12 months of therapy. Improvements ranged from −0.20 to −0.31 logMAR (2–3 ETDRS lines). One retrospective study compared the effect of idebenone in two subgroups according to time from LHON onset (1–5 years, n = 7; >5 years, n = 8) showing no difference between groups.ConclusionsData presented indicates a potential therapeutic effect of idebenone in chronic LHON patients, which may be explained by the reactivation of dysfunctional retinal ganglion cells and deserved further investigation.
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