Risk‐Benefit Value of Inhaled Glucocorticoids: A Pharmacokinetic/ Pharmacodynamic Perspective

Rohatagi, Shashank; Appajosyula, Sireesh; Derendorf, Hartmut; Szefler, Stanley J.; Nave, Ruediger; Zech, K.; Banerji, Donald

doi:10.1177/0091270003260334

Cited by 86 publications

(92 citation statements)

References 57 publications

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“…In addition, the high pulmonary deposition of ciclesonide and the high affinity of the active metabolite for the glucocorticoid receptor potentially contribute to the improvements in lung function and asthma symptoms. [23,24] Approximately 52% of the ciclesonide dose, administered via HFA-MDI, is delivered to the lungs, with the highest deposition (55% of the deposited dose) in the peripheral regions of the lung. [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.…”

Section: Discussionmentioning

confidence: 99%

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

Ukena

Biberger²,

Steinijans³

et al. 2007

Pulmonary Pharmacology & Therapeutics

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Background: Ciclesonide is a lung-activated inhaled corticosteroid that provides effective control of persistent asthma. The objective of this study was to compare the efficacy and safety of once-daily ciclesonide versus once-daily budesonide in patients with asthma. Methods:A total of 399 patients with asthma were randomised to receive once-daily ciclesonide 320 µg ex-actuator (equivalent to 400 µg ex-valve) or once-daily budesonide 400 µg for 12 weeks. The primary endpoint was forced expiratory volume in 1 second (FEV 1 ). Additional efficacy variables included forced vital capacity (FVC), peak expiratory flow (PEF), asthma symptoms, use of rescue medication and time to onset of effect. Adverse events were monitored throughout the study. Conclusion:Once-daily ciclesonide was more effective than once-daily budesonide in improving FEV 1 , FVC and PEF. Ciclesonide also had an earlier onset of action than budesonide in patients with persistent asthma. Both ciclesonide and budesonide had good safety and tolerability profiles.

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Section: Discussionmentioning

confidence: 99%

“…[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] …”

Section: Discussionmentioning

confidence: 99%

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

Ukena

Biberger²,

Steinijans³

et al. 2007

Pulmonary Pharmacology & Therapeutics

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“…Being inhalation half-life a critical property for an ICS as it relates to pulmonary retention time (i.e. the rate at which ICSs are absorbed across the pulmonary membranes and out of the airways) [40]. This is a disadvantage for mometasone because longer pulmonary retention is related to prolonged efficacy [40].…”

Section: Fluticasone Propionate and Formoterolmentioning

confidence: 99%

“…the rate at which ICSs are absorbed across the pulmonary membranes and out of the airways) [40]. This is a disadvantage for mometasone because longer pulmonary retention is related to prolonged efficacy [40]. Moreover, fluticasone propionate is the most lipophilically active ICS [35], and therefore has a long duration of anti-inflammatory action.…”

Section: Fluticasone Propionate and Formoterolmentioning

confidence: 99%

Fluticasone propionate/formoterol: A fixed-combination therapy with flexible dosage

Papi

Blasi

Canonica

et al. 2014

European Journal of Internal Medicine

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International guidelines describe asthma control as the main outcome of asthma management. Prevention of symptoms, improved quality of life, and reduction of exacerbations are the main components, consequently decreasing health care costs. However, many of these objectives remain unmet in real life: several surveys show that a large proportion of asthmatic patients are not well controlled despite the efficacy of current available treatment. Several randomized controlled clinical trials indicate that combining inhaled corticosteroids and long-acting β 2 -agonists, by means of a single inhaler, greatly improves the management of the disease. The results of 9 multicenter phase III clinical studies demonstrate that the fixed combination of fluticasone propionate/formoterol in a single inhaler is effective in terms of lung function and symptom control. These studies highlight the dose flexibility, safety and tolerability of this new inhaled combination. These characteristics meet the recommendations of international guidelines, and the preferences of respiratory physicians who identified these aspects as critical components of a successful asthma therapy. Combination of fluticasone propionate/formoterol in a single inhaler provides potent anti-inflammatory activity of fluticasone propionate and rapid onset of action of the β 2 -agonist formoterol making this association a viable treatment option both in terms of effectiveness and compliance.

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“…The 'ideal' pharmacokinetic (PK)/pharmacodynamic (PD) profile for an ICS in terms of optimal benefit-to-risk ratio comprises the following features: high pulmonary deposition; high receptor binding; prolonged pulmonary retention; marked lipid conjugation; minimal oral bioavailability; small particle size (< 5 µm); low pharyngeal deposition; high plasma protein binding; rapid metabolism and clearance from the plasma; and, therefore, low systemic concentration [62][63][64].…”

Section: Nebulized Bdpmentioning

confidence: 99%

Inhaled corticosteroid therapy with nebulized beclometasone dipropionate

Nicolini

Cremonesi

Melani

2010

Pulmonary Pharmacology & Therapeutics

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Inhaled corticosteroids (ICS) are the most effective anti-inflammatory agents for the management of chronic persistent asthma, and are therefore recommended as first-line antiasthmatic therapy in children and adults. In various settings, the administration of ICS via nebulizer rather than hand-held inhaler (HHI) may have certain advantages, as many patients with HHI fail to use these devices properly or efficiently. In particular, young children, the elderly, the acutely ill, and those with restricted dexterity may be unable to coordinate inhalation with actuation of the device or to generate sufficient inspiratory flow to operate breath-actuated devices effectively. Compliance with nebulized therapy may also be better than that with a pressurized metered-dose inhaler (pMDI) plus spacer. Systematic reviews conclude that there is no significant difference in clinical effects between nebulizers and HHI. Performance and clinical effect of nebulization are influenced by several technical aspects such as the nebulizer-drug combination, nebulizer type, output and lung deposition. Among the currently available ICS, nebulized beclometasone dipropionate (BDP) has been in clinical use for more than 35 years, and has demonstrated marked clinical efficacy and a favorable tolerability profile in children and adults with chronic persistent asthma. The clinical efficacy of nebulized beclometasone is discussed in the present review using data from 13 published studies, which included a total of 1250 patients. Three multicenter, randomized, double-blind studies showed that nebulized BDP is as effective as BDP via pMDI plus spacer in a 2:1 dose ratio. Controlled trials involving 497 adults and children demonstrated similar clinical efficacy between nebulized BDP and either nebulized fluticasone propionate or nebulized budesonide. In all these trials, treatment-related adverse effects were generally uncommon, most were mild to moderate in severity, and most were associated with the respiratory system. Metaanalyses show that BDP, like other inhaled corticosteroids, has no major influence on patient height, urinary cortisol concentration, or bone metabolism, thus suggesting the absence of growth retardation or any marked effect on adrenal function or the hypothalamic-pituitaryadrenal axis when used in the approved dose range. M A N U S C R I P T A C C E P T E D ARTICLE IN PRESSOverall, nebulized BDP appears to have a particularly important place in asthma therapy: as a general alternative to HHIs (e.g. in patients with poor HHI compliance); when patients such as children or the elderly are unable to operate HHIs because of poor hand-lung coordination, lack of cooperation, or low inspiratory flow rate; and when high dosages of ICS are required, such as in adults with severe, corticosteroid-dependent asthma.

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Risk‐Benefit Value of Inhaled Glucocorticoids: A Pharmacokinetic/ Pharmacodynamic Perspective

Cited by 86 publications

References 57 publications

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

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

Fluticasone propionate/formoterol: A fixed-combination therapy with flexible dosage

Inhaled corticosteroid therapy with nebulized beclometasone dipropionate

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