Inhaled budesonide and pulmonary sarcoidosis revisited.

Results of a few controlled clinical studies have been reported with inhaled corticosteroids (ICS) in patients with pulmonary sarcoidosis. Some evidence of efficacy has been observed, but mainly with the ICS budesonide (BUD). These clinically important and statistically significant results are restricted to maintenance therapy with BUD after induction of treatment with systemic corticosteroids for a few weeks or months.

Budesonide Attains Its Wide Clinical Profile by Alternative Kinetics.

The introduction of inhaled corticosteroids (ICSs) changed over a few decades the treatment focus of mild-to-moderate asthma from bronchodilation to reduction in inflammation. This was achieved by inhaling a suitable corticosteroid (CS), giving a high, protracted airway concentration at a low total dose, thereby better combining efficacy and tolerance than oral therapy. Successful trials with the potent, lipophilic "skin" CS beclomethasone dipropionate (BDP) paved the way, suggesting that ICSs require a very low water solubility, prolonging their intraluminal dissolution within airways.

May a different kinetic mode explain the high efficacy/safety profile of inhaled budesonide?

The claimed functional basis for ICSs in asthma and COPD is airway selectivity, attained by inhaling a potent, lipophilic compound with long local dissolution/absorption time. The development has been empirically based, resulting in five widely used ICSs. Among them, budesonide (BUD) deviates by being less lipophilic, leading to a more rapid systemic uptake with plasma peaks with some systemic anti-inflammatory activity.

Correction to: Benefit:Risk Profile of Budesonide in Obstructive Airways Disease.

Page 5, Fig. 2 Key milestones in the development of budesonide.

Benefit:Risk Profile of Budesonide in Obstructive Airways Disease.

Airway inflammation is a major contributing factor in both asthma and chronic obstructive pulmonary disease (COPD) and represents an important target for treatment. Inhaled corticosteroids (ICS) as monotherapy or in combination therapy with long-acting β-agonists or long-acting muscarinic antagonists are used extensively in the treatment of asthma and COPD. The development of ICS for their anti-inflammatory properties progressed through efforts to increase topical potency and minimise systemic potency and through advances in inhaled delivery technology.

20α- and 20β-dihydrocortisone may interfere in LC-MS/MS determination of cortisol in saliva and urine.

Background LC-MS/MS methods offer high selectivity in cortisol determinations. However, endogenous steroid metabolites may still interfere and compromise the results, for example in the diagnosis of Cushing's syndrome. Erroneously elevated cortisol may, in particular, be misleading at the low concentrations found in salivary samples obtained at late night and after dexamethasone suppression.

The role of intracellular esterification in budesonide once-daily dosing and airway selectivity.

Background: Since their introduction in the 1970s, inhaled corticosteroids (ICSs) have been used to control airway inflammation associated with asthma. Budesonide is one of the ICSs recommended as first-line therapy for mild to moderate persistent asthma.

Objective: This article describes the esterification of budesonide and how it results in prolonged, location-specific retention of drug in the airways, allowing once-daily dosing.

Design and synthesis of dihydrofolate reductase inhibitors encompassing a bridging ester group. Evaluation in a mouse colitis model.

Crohn's disease is a chronic inflammatory bowel disease characterized by inflammation of both the small and large intestines. Methotrexate (MTX), a classical dihydrofolate reductase (DHFR) inhibitor, has been used as a therapeutic agent in the treatment of patients with Crohn's disease in recent years. We sought to develop antifolates similar in structure to MTX that would be effective in reducing inflammation in a mouse disease model of colitis.

Budesonide fatty-acid esterification: a novel mechanism prolonging binding to airway tissue. Review of available data.

Aims: Evidence is accumulating that budesonide (BUD) forms intracellular esters in airways. which may affect both duration of action and therapeutic ratio of this drug. The aim of the present paper is to review the preclinical and human experimental evidence supporting the esterification of BUD, and to discuss the clinical implications this may have on asthma and rhinitis treatment.

Molecular mechanisms of decreased steroid responsiveness induced by latent adenoviral infection in allergic lung inflammation.

Background: We recently reported that allergic lung inflammation in guinea pigs became steroid resistant in the presence of latent adenoviral infection.

Objective: We sought to investigate the molecular mechanisms that underlie steroid resistance in adenoviral infection.

Methods: Guinea pigs with a latent adenoviral infection were sensitized and challenged with ovalbumin (OVA) and given daily injections of budesonide (20 mg/kg administered intraperitoneally).